Development of ~(18)F-labeled radiotracers for neuroreceptor imaging with positron emission tomography
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摘要
Positron emission tomography(PET)is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases.PET uses biomolecules as probes which are labeled with radionuclides of short half-lives,synthesized prior to the imaging studies.These probes are called radiotracers.Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min.The delivery of such radiotracers into the brain provides images of transport,metabolic,and neurotransmission processes on the molecular level.After a short introduction into the principles of PET,this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application.Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases,but also allow molecular neuroreceptor imaging studies in various small-animal models of disease,including geneticallyengineered animals.Furthermore,they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets,to investigate pathophysiology,to discover potential drug candidates,and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.
Positron emission tomography(PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases.PET uses biomolecules as probes which are labeled with radionuclides of short half-lives,synthesized prior to the imaging studies.These probes are called radiotracers.Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min.The delivery of such radiotracers into the brain provides images of transport,metabolic,and neurotransmission processes on the molecular level.After a short introduction into the principles of PET,this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application.Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases,but also allow molecular neuroreceptor imaging studies in various small-animal models of disease,including geneticallyengineered animals.Furthermore,they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets,to investigate pathophysiology,to discover potential drug candidates,and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.
Positron emission tomography(PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases.PET uses biomolecules as probes which are labeled with radionuclides of short half-lives,synthesized prior to the imaging studies.These probes are called radiotracers.Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min.The delivery of such radiotracers into the brain provides images of transport,metabolic,and neurotransmission processes on the molecular level.After a short introduction into the principles of PET,this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application.Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases,but also allow molecular neuroreceptor imaging studies in various small-animal models of disease,including geneticallyengineered animals.Furthermore,they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets,to investigate pathophysiology,to discover potential drug candidates,and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.
引文
[1]Mankoff DA.A definition of molecular imaging.J Nucl Med2007,48:18N,21N.
[2]Pichler BJ,Judenhofer MS,Pfannenberg C.Multimodal imaging approaches:PET/CT and PET/MRI.Handb Exp Pharmacol 2008:109-132.
[3]Drzezga A,Barthel H,Minoshima S,Sabri O.Potential clinical applications of PET/MR imaging in neurodegenerative diseases.J Nucl Med 2014,55:1-9.
[4]Levi H.George von Hevesy memorial lecture.George Hevesy and his concept of radioactive indicators—in retrospect.Eur J Nucl Med 1976,1:3-10.
[5]Sampson CD(Ed.).Textbook of Radiopharmacy:Theory and Practice.3rd.ed.Amsterdam:Gordan and Breach Science Publishers,1999.
[6]Brust P,Deuther-Conrad W,Donat CK,Barthel H,Riss P,Paterson L,et al.Preclinical aspects of nicotinic acetylcholine receptor imaging.In:Dierckx RAJ,Otte A,de Vries EFJ,et al.(Eds.).PET and SPECT of Neurobiological Systems.Springer,2014:465-512.
[7]Virdee K,Cumming P,Caprioli D,Jupp B,Rominger A,Aigbirhio Fl,et al.Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders.Neurosci Biobehav Rev 2012,36:1188-1216.
[8]Melhem M.Translation of central nervous system occupancy from animal models:application of pharmacokinetic/pharmacodynamic modeling.J Pharmacol Exp Ther 2013,347:2-6.
[9]Frey KA,Koeppe RA,Mulholland GK,Jewett D,Hichwa R,Ehrenkaufer RL,et al.In vivo muscarinic cholinergic receptor imaging in human brain with[~(11)C]scopolamine and positron emission tomography.J Cereb Blood Flow Metab 1992,12:147-154.
[10]Xie G,Gunn RN,Dagher A,Daloze T,Plourde G,Backman SB,et al.PET quantification of muscarinic cholinergic receptors with[N-11C-methyl]-benztropine and application to studies of propofol-induced unconsciousness in healthy human volunteers.Synapse 2004,51:91-101.
[11]Yamamoto S,Ouchi Y,Nakatsuka D,Tahara T,Mizuno K,Tajima S,et al.Reduction of[~(11)C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.PLoS One 2012,7:e51515.
[12]Ichise M,Cohen RM,Carson RE.Noninvasive estimation of normalized distribution volume:application to the muscarinic-2 ligand[~(18)F]FP-TZTP.J Cereb Blood Flow Metab2008,28:420-430.
[13]Sabri O,Kendziorra K,Wolf H,Gertz HJ,Brust P.Acetylcholine receptors in dementia and mild cognitive impairment.Eur J Nucl Med Mol Imaging 2008,35 Suppl 1:S30-45.
[14]Ding YS,Fowler JS,Logan J,Wang GJ,Telang F,Garza V,et al.6-[~(18)F]Fluoro-A-85380,a new PET tracer for the nicotinic acetylcholine receptor:studies in the human brain and in vivo demonstration of specific binding in white matter.Synapse 2004,53:184-189.
[15]Wong DF,Kuwabara H,Kim J,Brasic JR,Chamroonrat W,Gao Y,et al.PET imaging of high-affinityα_4β_2 nicotinic acetylcholine receptors in humans with 18F-AZAN,a radioligand with optimal brain kinetics.J Nucl Med 2013,54:1308-1314.
[16]Sabri O,Wilke S,Graf S,Schonknecht P,Becker G,Patt M,et al.Cerebralα_4β_2 nicotinic acetylcholine receptors(nAChRs)in early Alzheimer disease(AD)assessed with the new PET tracer(-)-[~(18)F]-norchloro-fluoro-homoepibatidine(NCFHEB).J Nucl Med 2011,52(Suppl.1):1267.
[17]Toyohara J,Sakata M,Wu J,Ishikawa M,Oda K,Ishii K,et al.Preclinical and the first clinical studies on[~(11)C]CHIBA-1001 for mapping a7 nicotinic receptors by positron emission tomography.Ann Nucl Med 2009,23:301-309.
[18]Bauer A,Holschbach MH,Meyer PT,Boy C,Herzog H,Olsson RA,et al.In vivo imaging of adenosine A,receptors in the human brain with[~(18)F]CPFPX and positron emission tomography.Neuroimage 2003,19:1760-1769.
[19]Fukumitsu N,Ishii K,Kimura Y,Oda K,Hashimoto M,Suzuki M,et al.Adenosine A,receptors using 8-dicyclopropylmethyl-1-[~(11)C]methyl-3-propylxanthine PET in Alzheimer's disease.Ann Nucl Med 2008,22:841-847.
[20]Mishina M,Ishiwata K,Naganawa M,Kimura Y,Kitamura S,Suzuki M,et al.Adenosine A_(2A)receptors measured with[~(11)C]TMSX PET in the striata of Parkinson's disease patients.PLoS One 2011,6:e17338.
[21]Ramlackhansingh AF,Bose SK,Ahmed I,Turkheimer FE,Pavese N,Brooks DJ.Adenosine 2_A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease.Neurology 2011,76:1811-1816.
[22]Burns HD,Van Laere K,Sanabria-Bohorquez S,Hamill TG,Bormans G,Eng WS,et al.[~(18)F]MK-9470,a positron emission tomography(PET)tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor.Proc Natl Acad Sci U S A 2007,104:9800-9805.
[23]Terry GE,Hirvonen J,Liow JS,Seneca N,Tauscher JT,Schaus JM,et al.Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography.Eur J Nucl Med Mol Imaging 2010,37:1499-1506.
[24]Wong DF,Kuwabara H,Horti AG,Raymont V,Brasic J,Guevara M,et al.Quantification of cerebral cannabinoid receptors subtype 1(CB1)in healthy subjects and schizophrenia by the novel PET radioligand[~(11)C]OMAR.Neuroimage 2010,52:1505-1513.
[25]Ahmad R,Koole M,Evens N,Serdons K,Verbruggen A,Bormans G,et al.Whole-body biodistribution and radiation dosimetry of the cannabinoid type 2 receptor ligand[~(11)C]-NE40 in healthy subjects.Mol Imaging Biol 2013.
[26]Farde L,Halldin C,Stone-Elander S,Sedvall G.PET analysis of human dopamine receptor subtypes using~(11)C-SCH 23390and~(11)C-raclopride.Psychopharmacology 1987,92:278-284.
[27]Karlsson P,Farde L,Halldin C,Swahn CG,Sedvall G,Foged C,et al.PET examination of[~(11)C]NNC 687 and[~(11)C]NNC 756 as new radioligands for the D,-dopamine receptor.Psychopharmacology 1993,113:149-156.
[28]Slifstein M,Kolachana B,Simpson EH,Tabares P,Cheng B,Duvall M,et al.COMT genotype predicts cortical-limbic D,receptor availability measured with[~(11)C]NNC112 and PET.Mol Psychiatry 2008,13:821-827.
[29]Farde L,Hall H,Ehrin E,Sedvall G.Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET.Science 1986,231:258-261.
[30]Wong DF,Wagner HN,Jr.,Tune LE,Dannals RF,Pearlson GD,Links JM,et al.Positron emission tomography reveals elevated D_2 dopamine receptors in drug-naive schizophrenics.Science 1986,234:1558-1563.
[31]Narendran R,Frankle WG,Mason NS,Laymon CM,Lopresti BJ,Price JC,et al.Positron emission tomography imaging of D~_(2/3)agonist binding in healthy human subjects with the radiotracer[~(11)C]-N-propyl-norapomorphine:preliminary evaluation and reproducibility studies.Synapse 2009,63:574-584.
[32]Otsuka T,Ito H,Halldin C,Takahashi H,Takano H,Arakawa R,et al.Quantitative PET analysis of the dopamine D_2 receptor agonist radioligand~(11)C-(R)-2-CH30-N-npropylnorapomorphine in the human brain.J Nucl Med 2009,50:703-710.
[33]Farde L,Suhara T,Nyberg S,Karlsson P,Nakashima Y,Hietala J,et al.A PET-study of[~(11)C]FLB 457 binding to extrastriatal D_2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients.Psychopharmacology1997,133:396-404.
[34]Mukherjee J,Christian BT,Dunigan KA,Shi B,Narayanan TK,Satter M,et al.Brain imaging of~(18)F-fallypride in normal volunteers:blood analysis,distribution,test-retest studies,and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors.Synapse 2002,46:170-188.
[35]Ginovart N,Willeit M,Rusjan P,Graff A,Bloomfield PM,Houle S,et al.Positron emission tomography quantification of[~(11)C]-(+)-PHNO binding in the human brain.J Cereb Blood Flow Metab 2007,27:857-871.
[36]Moresco RM,Scheithauer BW,Lucignani G,Lombardi D,Rocca A,Losa M,et al.Oestrogen receptors in meningiomas:a correlative PET and immunohistochemical study.Nucl Med Comm1997,18:606-615.
[37]Toyohara J,Sakata M,Fujinaga M,Yamasaki T,Oda K,Ishii K,et al.Preclinical and the first clinical studies on[~(11)C]ITMM for mapping metabotropic glutamate receptor subtype1 by positron emission tomography.Nucl Med Biol 2013,40:214-220.
[38]Ametamey SM,Treyer V,Streffer J,Wyss MT,Schmidt M,Blagoev M,et al.Human PET studies of metabotropic glutamate receptor subtype 5 with~(11)C-ABP688.J Nucl Med2007,48:247-252.
[39]Brown AK,Kimura Y,Zoghbi SS,Simeon FG,Liow JS,Kreisl WC,et al.Metabotropic glutamate subtype 5 receptors are quantified in the human brain with a novel radioligand for PET.J Nucl Med 2008,49:2042-2048.
[40]Kagedal M,Cselenyi Z,Nyberg S,Jonsson S,Raboisson P,Stenkrona P,et al.Non-linear mixed effects modelling of positron emission tomography data for simultaneous estimation of radioligand kinetics and occupancy in healthy volunteers.Neuroimage 2012,61:849-856.
[41]Wong DF,Waterhouse R,Kuwabara H,Kim J,Brasic JR,Chamroonrat W,et al.~(18)F-FPEB,a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors:a firstin-human study of radiochemical safety,biokinetics,and radiation dosimetry.J Nucl Med 2013,54:388-396.
[42]Kumlien E,Hartvig P,Valind S,Oye I,Tedroff J,Langstrdm B.NMDA-receptor activity visualized with(S)-[N-methyl-~(11)C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy.Epilepsia 1999,40:30-37.
[43]Hammers A,Asselin M,Brooks DJ,Luthra SK,Hume SP,Thompson PJ,et al.Correlation of memory function with binding of[C-11]CNS 5161,a novel putative NMDA ion channel PET ligand.Neuroimage 2004,22(Suppl 2):T54-55.
[44]Ametamey SM,Bruehlmeier M,Kneifel S,Kokic M,Honer M,Arigoni M,et al.PET studies of~(18)F-memantine in healthy volunteers.Nucl Med Biol 2002,29:227-231.
[45]McGinnity CJ,Hammers A,Riano Barros DA,Luthra SK,Jones PA,Trigg W,et al.Initial evaluation of~(18)F-GE-179,a putative PET Tracer for activated N-methyl D-aspartate receptors.J Nucl Med 2014,55:423-430.
[46]Matsumoto R,Haradahira T,Ito H,Fujimura Y,Seki C,Ikoma Y,et al.Measurement of glycine binding site of N-methylD-asparate receptors in living human brain using 4-acetoxy derivative of L-703,717,4-acetoxy-7-chloro-3-[3-(4-[~(11)C]methoxybenzyl)phenyl]-2(1H)-quinolone(AcL703)with positron emission tomography.Synapse 2007,61:795-800.
[47]Yanai K,Watanabe T,Itoh M,Hatazawa J,Iwata R,Ido T.Labeling of histamine H1-receptors in vivo:a compartment model analysis and positron emission tomographic imaging.Agents Actions Suppl 1991,33:381-386.
[48]Ashworth S,Rabiner EA,Gunn RN,Plisson C,Wilson AA,Comley RA,et al.Evaluation of~(11)C-GSK189254 as a novel radioligand for the H3 receptor in humans using PET.J Nucl Med 2010,51:1021-1029.
[49]Persson A,Ehrin E,Eriksson L,Farde L,Hedstr(o|¨)m CG,Litton JE,et al.Imaging of[~(11)C]-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography.J Psychiatric Res 1985,19:609-622.
[50]Leveque P,Sanabria-Bohorquez S,Bol A,De Voider A,Labar D,Van Rijckevorsel K,et al.Quantification of human brain benzodiazepine receptors using[~(18)F]fluoroethylflumazenil:a first report in volunteers and epileptic patients.Eur J Nucl Med Mol Imaging 2003,30:1630-1636.
[51]Lee JD,Park HJ,Park ES,Kim DG,Rha DW,Kim EY,et al.Assessment of regional GABA_A receptor binding using~(18)F-fluoroflumazenil positron emission tomography in spastic type cerebral palsy.Neuroimage 2007,34:19-25.
[52]Massaweh G,Schirrmacher E,la Fougere C,Kovacevic M,Wangler C,Jolly D,et al.Improved work-up procedure for the production of[~(18)F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke.Nucl Med Biol 2009,36:721-727.
[53]Lingford-Hughes A,Hume SP,Feeney A,Hirani E,Osman S,Cunningham VJ,et al.Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with[~(11)C]Ro15 4513 positron emission tomography.J Cereb Blood Flow Metab 2002,22:878-889.
[54]Frost JJ,Mayberg HS,Sadzot B,Dannals RF,Lever JR,Ravert HT,et al.Comparison of[~(11)C]diprenorphine and[~(11)C]carfentanil binding to opiate receptors in humans by positron emission tomography.J Cereb Blood Flow Metab 1990,10:484-492.
[55]Madar I,Lesser RP,Krauss G,Zubieta JK,Lever JR,Kinter CM,et al.Imaging of a-and u-opioid receptors in temporal lobe epilepsy by positron emission tomography.Ann Neurol1997,41:358-367.
[56]Tomasi G,Zheng M-Q,Weinzimmer D,Lin S-F,Nabulsi N,Williams W,et al.Kinetic modeling of the kappa agonist tracer[~(11)C]GR103545 in humans.J Nucl Med 2010,51(Supplement 2):1293.
[57]Cohen RM,Carson RE,Sunderland T.Opiate receptor avidity in the thalamus is sexually dimorphic in the elderly.Synapse2000,38:226-229.
[58]Baumgartner U,Buchholz HG,Bellosevich A,Magerl W,Siessmeier T,Rolke R,et al.High opiate receptor binding potential in the human lateral pain system.Neuroimage2006,30:692-699.
[59]Hostetler ED,Sanabria-Bohorquez S,Fan H,Zeng Z,Gantert L,Williams M,et al.Synthesis,characterization,and monkey positron emission tomography(PET)studies of[~(18)F]Y1-973,a PET tracer for the neuropeptide Y Y,receptor.Neuroimage2011,54:2635-2642.
[60]Pike VW,McCarron JA,Lammerstma AA,Hume SP,Poole K,Grasby PM,et al.First delineation of 5-HT_(1A)receptors in human brain with PET and"C WAY-100635.Eur J Pharmacol 1995,283:R1-3.
[61]Parsey RV,Slifstein M,Hwang DR,Abi-Dargham A,Simpson N,Mawlawi O,et al.Validation and reproducibility of measurement of 5-HT_(1A)receptor parameters with[carbonyl-~(11)C]WAY-100635 in humans:comparison of arterial and reference tisssue input functions.J Cereb Blood Flow Metab2000,20:1111-1133.
[62]Andree B,Halldin C,Pike VW,Gunn RN,Olsson H,Farde L.The PET radioligand[carbonyl-~(11)C]desmethyl-WAY-100635binds to 5-HT_(1A)receptors and provides a higher radioactive signal than[carbonyl-~(11)C]WAY-100635 in the human brain.J Nucl Med 2002,43:292-303.
[63]Houle S,Wilson AA,Inaba T,Fisher N,DaSilva JN.Imaging5-HT_(1A)receptors with positron emission tomography:initial human studies with[~(11)C]CPC-222.Nucl Med Comm 1997,18:1130-1134.
[64]Milak MS,DeLorenzo C,Zanderigo F,Prabhakaran J,Kumar JS,Majo VJ,et al.In vivo quantification of human serotonin1A receptor using~(11)C-CUMI-101,an agonist PET radiotracer.J Nucl Med 2010,51:1892-1900.
[65]Costes N,Merlet I,Zimmer L,Lavenne F,Cinotti L,Delforge J,et al.Modeling[~(18)F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine_(1A)receptor concentration with multiinjection.J Cereb Blood Flow Metab 2002,22:753-765.
[66]Theodore WH,Giovacchini G,Bonwetsch R,Bagic A,Reeves-Tyer P,Herscovitch P,et al.The effect of antiepileptic drugs on 5-HT-receptor binding measured by positron emission tomography.Epilepsia 2006,47:499-503.
[67]Gallezot JD,Nabulsi N,Neumeister A,Planeta-Wilson B,Williams WA,Singhal T,et al.Kinetic modeling of the serotonin 5-HT_(1BN)receptor radioligand[~(11)C]P943 in humans.J Cereb Blood Flow Metab 2010,30:196-210.
[68]Varnas K,Nyberg S,Halldin C,Varrone A,Takano A,Karlsson P,et al.Quantitative analysis of[~(11)C]AZ10419369binding to 5-HT_(1B)receptors in human brain.J Cereb Blood Flow Metab 2011,31:113-123.
[69]Murrough JW,Henry S,Hu J,Gallezot JD,Planeta-Wilson B,Neumaier JF,et al.Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.Psychopharmacology 2011,213:547-553.
[70]Hinz R,Bhagwagar Z,Cowen PJ,Cunningham VJ,Grasby PM.Validation of a tracer kinetic model for the quantification of 5-HT_(2A)receptors in human brain with[~(11)C]MDL 100,907.J Cereb Blood Flow Metab 2007,27:161-172.
[71]Rosier A,Dupont P,Peuskens J,Bormans G,Vandenberghe R,Maes M,et al.Visualisation of loss of 5-HT_(2A)receptors with age in healthy volunteers using[~(18)F]altanserin and positron emission tomographic imaging.Psychiatry Res1996,68:11-22.
[72]van Dyck CH,Soares JC,Tan PZ,Staley JK,Baldwin RM,Amici LA,et al.Equilibrium modeling of 5-HT_(2A)receptors with[~(18)F]deuteroaltanserin and PET:feasibility of a constant infusion paradigm.Nucl Med Biol 2000,27:715-722.
[73]Trichard C,Paillere-Martinot ML,Attar-Levy D,Recassens C,Monnet F,Martinot JL.Binding of antipsychotic drugs to cortical 5-HT_(2A)receptors:a PET study of chlorpromazine,clozapine,and amisulpride in schizophrenic patients.Am J Psychiatry 1998,155:505-508.
[74]Ettrup A,da Cunha-Bang S,McMahon B,Lehel S,Dyssegaard A,Skibsted AW,et al.Serotonin 2_A receptor agonist binding in the human brain with[~(11)C]Cimbi-36.J Cereb Blood Flow Metab 2014.
[75]Marner L,Gillings N,Comley RA,Baare WF,Rabiner EA,Wilson AA,et al.Kinetic modeling of~(11)C-SB207145 binding to 5-HT_4 receptors in the human brain in vivo.J Nucl Med2009,50:900-908.
[76]Parker CA,Gunn RN,Rabiner EA,Slifstein M,Comley R,Salinas C,et al.Radiosynthesis and characterization of~(11)C-GSK215083 as a PET radioligand for the 5-HT_6 receptor.J Nucl Med 2012,53:295-303.
[77]Mishina M,Ishiwata K,Ishii K,Kitamura S,Kimura Y,Kawamura K,et al.Function of sigmal receptors in Parkinson's disease.Acta Neurol Scand 2005 112:103-107.
[78]Waterhouse RN,Nobler MS,Zhou Y,Chang RC,Morales O,Kuwabara H,et al.First evaluation of the sigmal receptor radioligand[~(18)F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine([~(18)F]FPS)in healthy humans.Neuroimage 2004,22:T29.
[79]Junck L,Olson JM,Ciliax BJ,Koeppe RA,Watkins GL,Jewett DM,et al.PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site.Ann Neurol1989,26:752-758.
[80]Banati RB,Goerres GW,Myers R,Gunn RN,Turkheimer FE,Kreutzberg GW,et al.[~(11)C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis.Neurology 1999,53:2199-2203.
[81]Brown AK,Fujita M,Fujimura Y,Liow JS,Stabin M,Ryu YH,et al.Radiation dosimetry and biodistribution in monkey and man of~(11)C-PBR28:a PET radioligand to image inflammation.J Nucl Med 2007,48:2072-2079.
[82]Endres CJ,Pomper MG,James M,Uzuner O,Hammoud DA,Watkins CC,et al.Initial evaluation of~(11)C-DPA-713,a novel TSPO PET ligand,in humans.J Nucl Med 2009,50:1276-1282.
[83]Yasuno F,Kosaka J,Ota M,Higuchi M,Ito H,Fujimura Y,et al.Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with[~(11)C]DAA1106.Psychiatry Res 2012,203:67-74.
[84]Gulyas B,Toth M,Schain M,Airaksinen A,Vas A,Kostulas K,et al.Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke:a PET study with the TSPO molecular imaging biomarker[~(11)C]vinpocetine.J Neurol Sci2012,320:110-117.
[85]Fujimura Y,Zoghbi SS,Simeon FG,Taku A,Pike VW,Innis RB,et al.Quantification of translocator protein(18 kDa)in the human brain with PET and a novel radioligand,F-18-PBR06.J Nucl Med 2009,50:1047-1053.
[86]Arlicot N,Vercouillie J,Ribeiro MJ,Tauber C,Venel Y,Baulieu JL,et al.Initial evaluation in healthy humans of[~(18)F]DPA-714,a potential PET biomarker for neuroinflammation.Nucl Med Biol 2012,39:570-578.
[87]Mizrahi R,Rusjan PM,Kennedy J,Pollock B,Mulsant B,Suridjan I,et al.Translocator protein(18 kDa)polymorphism(rs6971)explains in-vivo brain binding affinity of the PET radioligand[~(18)F]FEPPA.J Cereb Blood Flow Metab 2012,32:968-972.
[88]Guo Q,Colasanti A,Owen DR,Onega M,Kamalakaran A,Bennacef I,et al.Quantification of the specific translocator protein signal of~(18)F-PBR111 in healthy humans:a genetic polymorphism effect on in vivo binding.J Nucl Med 2013,54:1915-1923.
[89]Brust P,Deuther-Conrad W,Lehmkuhl K,Jia H,Wunsch B.Molecular imaging of a,receptors in vivo:current status and perspectives.Curr Med Chem 2014,21:35-69.
[90]Jansen KL,Faull RL,Storey P,Leslie RA.Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss.Brain Res 1993,623:299-302.
[91]Weissman AD,Casanova MF,Kleinman JE,London ED,De Souza EB.Selective loss of cerebral cortical sigma,but not PCP binding sites in schizophrenia.Biol Psychiatry 1991,29:41-54.
[92]van Waarde A,Rybczynska AA,Ramakrishnan N,Ishiwata K,Elsinga PH,Dierckx RA.Sigma receptors in oncology:therapeutic and diagnostic applications of sigma ligands.Curr Pharm Des 2010,16:3519-3537.
[93]Banister SD,Kassiou M.The therapeutic potential of sigma(a)receptors for the treatment of central nervous system diseases:evaluation of the evidence.Curr Pharm Des 2012,18:884-901.
[94]Megalizzi V,Le Mercier M,Decaestecker C.Sigma receptors and their ligands in cancer biology:overview and new perspectives for cancer therapy.Med Res Rev 2012,32:410-427.
[95]Schliebs R,Arendt T.The cholinergic system in aging and neuronal degeneration.Behav Brain Res 2011,221:555-563.
[96]Brust P,Deuther-Conrad W.Molecular imaging of a7nicotinic acetylcholine receptors in vivo:current status and perspectives.In:Bright P(Ed).Neuroimaging-Clinical Applications.InTech,2012:533-558.
[97]Brust P,Peters D,Deuther-Conrad W.Development of radioligands for the imaging ofα7 nicotinic acetylcholine receptors with positron emission tomography.Curr Drug Targets 2012,13:594-601.
[98]Kadir A,Almkvist O,Wall A,Langstrom B,Nordberg A.PET imaging of cortical~(11)C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease.Psychopharmacology 2006,188:509-520.
[99]Papke RL.Merging old and new perspectives on nicotinic acetylcholine receptors.Biochem Pharmacol 2014.doi:10.1016/j.bcp.2014.1001.1029.
[100]Moerlein SM.Molecular imaging and the development of new radiopharmaceuticals.In:Kowalsky RJ,Falen SW(Eds.).Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine.American Pharmacists Association(APhA),2011:741.
[101]Davenport AP,Russel FD.Radioligand Binding Assays:Theory and Practice.In:Mather SJ(Ed.).Current Directions in Radiopharmaceutical Research and Development.Kluwer Academic Publisher,1996:169-179.
[102]Koeppe RA.A panel discussion on the future of pharmacology and experimental tomography.In:Gjedde A,Hansen SB,Knudsen GM,Paulson OB(Eds.).Physiological Imaging of the Brain with PET.Academic Press,2001:402.
[103]Hurst R,Rollema H,Bertrand D.Nicotinic acetylcholine receptors:from basic science to therapeutics.Pharmacol Ther 2013,137:22-54.
[104]Lendvai B,Kassai F,Szajli A,Nemethy Z.alpha7 Nicotinic acetylcholine receptors and their role in cognition.Brain Res Bull 2013,93:86-96.
[105]Sorger D,Scheunemann M,Vercouillie J,Grossmann U,Fischer S,Hiller A,et al.Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[~(18)F]fluoro-benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydrobenzo[1,4]oxazines.Nucl Med Biol 2009,36:17-27.
[106]Giboureau N,Som IM,Boucher-Arnold A,Guilloteau D,Kassiou M.PET radioligands for the vesicular acetylcholine transporter(VAChT).Curr Top Med Chem 2010,10:1569-1583.
[107]Fujita M,Innis RB.In vivo molecular imaging:ligand development and research applications.In:Borroni E and Kupfer DJ(Eds.).Neuropsychopharmacology:The Fifth Generation of Progress.New York:Raven Press Ltd,2002,Section 3:411-425.
[108]Blower PJ.Microautoradiography.In:Mather SJ(Ed.).Current Directions in Radiopharmaceutical Research and Development.Kluwer Academic Publisher,1996:219-232.
[109]Lapchak PA,Araujo DM,Hefti F.Effects of chronic nerve growth factor treatment on hippocampal[3H]cytisine/nicotinic binding sites and presynaptic nicotinic receptor function following fimbrial transections.Neuroscience 1994,60:293-298.
[110]Rubboli F,Court JA,Sala C,Morris C,Perry E,Clementi F.Distribution of neuronal nicotinic receptor subunits in human brain.Neurochem Int 1994,25:69-71.
[111]Baddick CG,Marks MJ.An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants.Biochem Pharmacol 2011,82:828-841.
[112]Morley BJ,Kemp GE,Salvaterra P.a-Bungarotoxin binding sites in the CNS.Life Sci 1979,24:859-872.
[113]Whiteaker P,Davies AR,Marks MJ,Blagbrough IS,Potter BV,Wolstenholme AJ,et al.An autoradiographic study of the distribution of binding sites for the novelα7-selective nicotinic radioligand[~3H]-methyllycaconitine in the mouse brain.Eur J Neurosci 1999,11:2689-2696.
[114]Deuther-Conrad W,Fischer S,Hiller A,Nielsen EO,Timmermann DB,Steinbach J,et al.Molecular imaging of al nicotinic acetylcholine receptors:design and evaluation of the potent radioligand[~(18)F]NS10743.Eur J Nucl Med Mol Imaging 2009,36:791-800.
[115]Daly JW.Thirty years of discovering arthropod alkaloids in amphibian skin.J Nat Prod 1998,61:162-172.
[116]Avalos M,Parker MJ,Maddox FN,Carroll Fl,Luetje CW.Effects of pyridine ring substitutions on affinity,efficacy,and subtype selectivity of neuronal nicotinic receptor agonist epibatidine.J Pharmacol Exp Ther 2002,302:1246-1252.
[117]Deuther-Conrad W,Patt JT,Feuerbach D,Wegner F,Brust P,Steinbach J.Norchloro-fluoro-homoepibatidine:specificity to neuronal nicotinic acetylcholine receptor subtypes in vitro.Farmaco 2004,59:785-792.
[118]Deuther-Conrad W,Patt JT,Lockman PR,Allen DD,Patt M,Schildan A,et al.Norchloro-fluoro-homoepibatidine(NCFHEB)-A promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET.Eur Neuropsychopharmacol 2008,18:222-229.
[119]Smits R,Fischer S,Hiller A,Deuther-Conrad W,Wenzel B,Patt M,et al.Synthesis and biological evaluation of both enantiomers of[~(18)F]flubatine,promising radiotracers with fast kinetics for the imaging ofα_4β_2-nicotinic acetylcholine receptors.Bioorg Med Chem 2014,22:804-812.
[120]Patt JT,Spang JE,Westera G,Buck A,Schubiger PA.Synthesis and in Vivo studies of[C-11]N-methylepibatidine:comparison of the stereoisomers.Nucl Med Biol 1999,26:165-173.
[121]Molina PE,Ding YS,Carroll Fl,Liang F,Volkow ND,Pappas N,et al.Fluoro-norchloroepibatidine:preclinical assessment of acute toxicity.Nucl Med Biol 1997,24:743-747.
[122]Gandiha A,Marshall IG.The effects of 2-(4-phenylpiperidino)-cyclohexanol(AH5183)on the acetylcholine content of,and output from,the chick biventer cervicis muscle preparation.Int J Neurosci 1973,5:191-196.
[123]Prior C,Marshall IG,Parsons SM.The pharmacology of vesamicol:an inhibitor of the vesicular acetylcholine transporter.Gen Pharmacol 1992,23:1017-1022.
[124]Hicks BW,Rogers GA,Parsons SM.Purification and characterization of a nonvesicular vesamicol-binding protein from electric organ and demonstration of a related protein in mammalian brain.J Neurochem 1991,57:509-519.
[125]Kovac M,Mavel S,Deuther-Conrad W,Meheux N,Glockner J,Wenzel B,et al.3D QSAR study,synthesis,and in vitro evaluation of(+)-5-FBVM as potential PET radioligand for the vesicular acetylcholine transporter(VAChT).Bioorg Med Chem 2010,18:7659-7667.
[126]Mulholland GK,Jung YW,Wieland DM,Kilbourn MR,Kuhl DE.Synthesis of[~(18)F]fluoroethoxy-benzovesamicol,a radiotracer for cholinergic neurons.J Labelled Comp Radiopharm 1993,33:583-591.
[127]Petrou M,Frey KA,Kilbourn MR,Scott PJ,Raffel DM,Bohnen Nl,et al.In vivo imaging of human cholinergic nerve terminals with(-)-5-~(18)F-fluoroethoxybenzovesamicol:biodistribution,dosimetry,and tracer kinetic analyses.J Nucl Med 2014.doi:10.2967/jnumed.113.124792.
[128]Parent MJ,Bedard MA,Aliaga A,Minuzzi L,Mechawar N,Soucy JP,et al.Cholinergic depletion in Alzheimer's disease shown by[~(18)F]FEOBV autoradiography.Int J Mol Imaging2013,2013:205045.
[129]Szymoszek A,Wenzel B,Scheunemann M,Steinbach J,Schuurmann G.First CoMFA characterization of vesamicol analogs as ligands for the vesicular acetylcholine transporter.J Med Chem 2008,51:2128-2136.
[130]Maier CA,Wiinsch B.Novel spiropiperidines as highly potent and subtype selectiveσ-receptor ligands.Part 1.J Med Chem 2002,45:438-448.
[131]Maier CA,Wunsch B.Novel s receptor ligands.Part 2.SAR of spiro[[2]benzopyran-1,4'-piperidines]and spiro[[2]benzofuran-1,4'-piperidines]with carbon substituents in position 3.J Med Chem 2002,45:4923-4930.
[132]Maier CA,Wunsch B.Novel s receptor ligands,Part 3:Synthesis and SAR studies of 3-substituted 1'-benzylspiro[[2]benzoxepine-1,4'-piperidines].Eur J Org Chem 2003:714-720.
[133]Grolie Maestrup E,Fischer S,Wiese C,Schepmann D,Hiller A,Deuther-Conrad W,et al.Evaluation of spirocyclic3-(3-fluoropropyl)-2-benzofurans as a,receptor ligands for neuroimaging with positron emission tomography.J Med Chem 2009,52:6062-6072.
[134]Gro(?)e Maestrup E,Wiese C,Schepmann D,Brust P,W(u|¨)nsch B.Synthesis,pharmacological activity and structure affinity relationships of spirocyclic a,receptor ligands with a(2-fluoroethyl)residue in 3-position.Bioorg Med Chem 2011,19:393-405.
[135]Grolie Maestrup E,Wiese C,Schepmann D,Hiller A,Fischer S,Scheunemann M,et al.Synthesis of spirocyclic sigma(1)receptor ligands as potential PET radiotracers,structureaffinity relationships and in vitro metabolic stability.Bioorg Med Chem 2009,17:3630-3641.
[136]Holl K,Falck E,K(o|¨)hler J,Schepmann D,Humpf HU,Brust P,et al.Synthesis,characterization,and metabolism studies of fluspidine enantiomers.Chem Med Chem 2013,8:2047-2056.
[137]Maisonial A,Grosse Maestrup E,Fischer S,Hiller A,Scheunemann M,Wiese C,et al.A~(18)F-labeled fluorobutylsubstituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of a,receptors.Chem Med Chem 2011,6:1401-1410.
[138]Maisonial A,Grosse Maestrup E,Wiese C,Hiller A,Schepmann D,Fischer S,et al.Synthesis,radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for centralσ_1 receptors and comparison with fluoroalkyl homologs.Bioorg Med Chem 2012,20:257-269.
[139]Fischer S,Wiese C,Grosse Maestrup E,Hiller A,DeutherConrad W,Scheunemann M,et al.Molecular imaging of sigma receptors:synthesis and evaluation of the potentσ_1selective radioligand[~(18)F]fluspidine.Eur J Nucl Med Mol Imaging 2011,38:540-551.
[140]Bickel U.How to measure drug transport across the bloodbrain barrier.NeuroRx 2005,2:15-26.
[141]Pardridge WM.Drug transport across the blood-brain barrier.J Cereb Blood Flow Metab 2012,32:1959-1972.
[142]Kessler RM,Ansari MS,de Paulis T,Schmidt DE,Clanton JA,Smith HE,et al.High affinity dopamine D_2 receptor radioligands.1.Regional rat brain distribution of iodinated benzamides.J Nucl Med 1991,32:1593-1600.
[143]Tsuji A.Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems.NeuroRx2005,2:54-62.
[144]Ecker GF,Noe CR.In silico prediction models for blood-brain barrier permeation.Curr Med Chem 2004,11:1617-1628.
[145]Gouverneur V,Miiller K.Fluorine in Pharmaceutical and Medicinal Chemistry:From Biophysical Aspects to Clinical Applications.Singapore:World Scientific Publishing 2012.
[146]Tressaud A,Haufe G(Eds.).Fluorine and Health,Molecular Imaging,Biomedical Materials and Pharmaceuticals.Elsevier Science,2008.
[147]Alauddin MM.Positron emission tomography(PET)imaging with~(18)F-based radiotracers.Am J Nucl Med Mol Imaging2012,2:55-76.
[148]Ross TL,Wester HJ.~(18)F:Labeling chemistry and labeled compounds.In:Vertes A,Nagy S,Klencsar Z,Lovas R,Rosch F(Eds.).Handbook of Nuclear Chemistry:Radiochemistry and Radiopharmaceutical Chemistry in Life Sciences,2nd Ed.Springer,2011,4:2021-2071.
[149]Schubiger PA,Lehmann L,Friebe M.PET Chemistry:The Driving Force in Molecular Imaging.Springer,2007.
[150]Bergman J,Solin O.Fluorine-18-labeled fluorine gas for synthesis of tracer molecules.Nucl Med Biol 1997,24:677-683.
[151]Forsback S,Marjamaki P,Eskola O,Bergman J,Rokka J,Gronroos T,et al.[~(18)F]CFT synthesis and binding to monoamine transporters in rats.EJNMMI Res 2012,2:3.
[152]Ermisch A,Brust P,Kretzschmar R,Ruhle HJ.Peptides and Blood-Brain Barrier Transport.Physiol Rev 1993,73:489-527.
[153]Coenen HH,Hamacher K,Sch(u|¨)IIer M,Stocklin G,Klatte B,Kn(o|¨)chel A.Process for the preparation of fluorine-18 labelled compounds by nucleophilic exchange.EP0167103 A2,1985.
[154]Coenen HH,Colosimo M,Schuller M,Stocklin G.Preparation of n.c.a.[~(18)F]CH_2BrF via aminopolyether supported nucleophilic substitution.J Labelled Compd Radiopharm1986,23:587-595.
[155]Roeda D,Dolle F.Aliphatic nucleophilic radiofluorination.Curr Radiopharm 2010,3:81-108
[156]Cai LS,Lu SY,Pike VW.Chemistry with[~(18)F]fluoride ion.European J Org Chem 2008:2853-2873.
[157]Hoepping A,Scheunemann M,Fischer S,DeutherConrad W,Hiller A,Wegner F,et al.Radiosynthesis and biological evaluation of an~(18)F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon.Nucl Med Biol 2007,34:559-570.
[158]Deuther-Conrad W,Fischer S,Scheunemann M,Hiller A,Diekers M,Friemel A,et al.GABA_A receptor specific pyrazolopyrimidines as potential imaging agents:In vivo characteristics of a new~(18)F-labelled Indiplon derivative.Curr Radiopharm 2009,2:24-31.
[159]Fischer S,Hiller A,Scheunemann M,Deuther-Conrad W,Hoepping A,Diekers M,et al.Radiosynthesis of novel1aF-labelled derivatives of indiplon as potential GABA_A receptor imaging tracers for PET.J Labelled Comp Radiopharm 2008,51:123-131.
[160]Schirrmacher R,Bradtmoller G,Schirrmacher E,Thews O,Tillmanns J,Siessmeier T,et al.~(18)F-labeling of peptides by means of an organosilicon-based fluoride acceptor.Angew Chem Int Ed Engl 2006,45:6047-6050.
[161]R6mer J,Fuchtner F,Steinbach J,Kasch H.Automated synthesis of 16a-[~(18)F]fluoroestradiol-3,17β-disulphamate.Appl Radiat Isot 2001,55:631-639.
[162]Ermert J,Coenen HH.Nucleophilic~(18)F-fluorination of complex molecules in activated carbocyclic aromatic position.Curr Radiopharm 2010,3:109-126
[163]Fischer S,Hiller A,Smits R,Hoepping A,Funke U,Wenzel B,et al.Radiosynthesis of racemic and enantiomerically pure(-)-[~(18)F]flubatine-A promising PET radiotracer for neuroimaging ofα_4β_2 nicotinic acetylcholine receptors.Appl Radiat Isot 2013,74C:128-136.
[164]Patt JT,Deuther-Conrad W,Wohlfarth K,Feuerbach D,Brust P,Steinbach J.Norchloro-fluoro-homoepibatidine:~(18)F-labelling and evaluation of affinity and selectivity at neuronal nicotinic acetylcholine receptors.J Labelled Compd Radiopharm 2003,46(S1):S 168.
[165]Patt M,Schildan A,Habermann B,Fischer S,Hiller A,Deuther-Conrad W,et al.Fully automated radiosynthesis of both enantiomers of[~(18)F]Flubatine under GMP conditions for human application.Appl Radiat Isot 2013,80:7-11.
[166]Hockley BG,Stewart MN,Sherman P,Quesada C,Kilbourn MR,Albin RL,et al.(-)-[~(18)F]Flubatine:evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use.J Labelled Comp Radiopharm 2013,56:595-599.
[167]Ruhl T,Deuther-Conrad W,Fischer S,Gunther R,Hennig L,Krautscheid H,et al.Cannabinoid receptor type 2(CB_2)-selective N-aryl-oxadiazolyl-propionamides:synthesis,radiolabelling,molecular modelling and biological evaluation.Org Med Chem Lett 2012,2:32.
[168]Teodoro R,Moldovan RP,Lueg C,Gunther R,Donat CK,Ludwig FA,et al.Radiofluorination and biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB_2 receptors.Org Med Chem Lett 2013,3:11.
[169]Loser R,Fischer S,Hiller A,Kckerling M,Funke U,Maisonial A,et al.Use of 3-[~(18)F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines:Investigation of precursor molecules,labelling conditions and enzymatic stability of the corresponding sulfonamides.Beilstein J Org Chem 2013,9:1002-1011.
[170]Wüst F,Khler L,Berndt M,Pietzsch J.Systematic comparison of two novel,thiol-reactive prosthetic groups for~(18)F labeling of peptides and proteins with the acylation agent succinimidyl-4-[~(18)F]fluorobenzoate([~(18)F]SFB).Amino Acids2009,36:283-295.
[171]Serdons K,Verbruggen A,Bormans GM.Developing new molecular imaging probes for PET.Methods 2009,48:104-111.
[172]Pretze M,Kuchar M,Bergmann R,Steinbach J,Pietzsch J,Mamat C.An efficient bioorthogonal strategy using CuAAC click chemistry for radiofluorinations of SNEW peptides and the role of copper depletion.Chem Med Chem 2013,8:935-945.
[173]Pretze M,Pietzsch D,Mamat C.Recent trends in bioorthogonal click-radiolabeling reactions using fluorine-18.Molecules 2013,18:8618-8665.
[174]Ramenda T,Kniess T,Bergmann R,Steinbach J,Wiist F.Radiolabelling of proteins with fluorine-18 via click chemistry.Chem Commun(Camb)2009:7521-7523.
[175]Ramenda T,Steinbach J,Wust F.4-[~(18)F]Fluoro-N-methylN-(propyl-2-yn-1-yl)benzenesulfonamide([~(18)F]F-SA):a versatile building block for labeling of peptides,proteins and oligonucleotides with fluorine-18 via Cu(l)-mediated click chemistry.Amino Acids 2013,44:1167-1180.
[176]Kniess T,Laube M,Bergmann R,Sehn F,Graf F,Steinbach J,et al.Radiosynthesis of a~(18)F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2(COX-2)in vitro and in vivo.Bioorg Med Chem 2012,20:3410-3421.
[177]Funke U,Fischer S,Hiller A,Scheunemann M,DeutherConrad W,Brust P,et al.3-(4-(6-Fluoroalkoxy-3,4-dihydroisoquinoline-2(1 H)-yl)cyclohexyl)-1 H-indol e-5-carbonitriles for SERT imaging:chemical synthesis,evaluation in vitro and radiofluorination.Bioorg Med Chem Lett 2008,18:4727-4730.
[178]Funke U,Schwan G,Maisonial A,Scheunemann M,Deuther-Conrad W,Fischer S,et al.Radiosynthesis and radiotracer properties of a 7-(2-[~(18)F]fluoroethoxy)-6-methoxypyrrolidinylquinazoline for imaging of phosphodiesterase 10A with PET.Pharmaceuticals(Basel)2012,5:169-188.
[179]Sorger D,Scheunemann M,Grossmann U,Fischer S,Vercouille J,Hiller A,et al.A new~(18)F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter.Nucl Med Biol 2008,35:185-195.
[180]Hoepping A,Scheunemann M,Fischer S,DeutherConrad W,Hiller A,Wegner F,et al.Radiosynthesis and biological evaluation of an~(18)F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon.Nucl Med Biol 2007,34:559-570.
[181]Donat CK,Schuhmann MU,Voigt C,Nieber K,DeutherConrad W,Brust P.Time-dependent alterations of cholinergic markers after experimental traumatic brain injury.Brain Res2008,1246:167-177.
[182]Perry DC,Kellar KJ.[3H]epibatidine labels nicotinic receptors in rat brain:an autoradiographic study.J Pharmacol Exp Ther1995,275:1030-1034.
[183]Vaupel DB,Mukhin AG,Kimes AS,Horti AG,Koren AO,London ED.In vivo studies with[125l]5-l-A-85380,a nicotinic acetylcholine receptor radioligand.Neuroreport 1998,9:2311-2317.
[184]Davies AR,Hardick DJ,Blagbrough IS,Potter BV,Wolstenholme AJ,Wonnacott S.Characterisation of the binding of[3H]methyllycaconitine:a new radioligand for labelling a7-type neuronal nicotinic acetylcholine receptors.Neuropharmacology 1999,38:679-690.
[185]No-authors-listed.Indiplon.Indiplon modified-release,indiplon MR,NBI 34060,NBI 34060 modified-release,NBI34060 MR.Drugs R D 2002,3:197-199.
[186]Hoepping A,Diekers M,Deuther-Conrad W,Scheunemann M,Fischer S,Hiller A,et al.Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors.Bioorg Med Chem 2008,16:1184-1194.
[187]Brust P,Scheffel U,Szabo Z.Radioligands for the study of the 5-HT transporter in vivo.IDrugs 1999,2:129-145.
[188]Kretzschmar M,Brust P,Zessin J,Cumming P,Bergmann R,Johannsen B.Autoradiographic imaging of the serotonin transporter in the brain of rats and pigs using S-([~(18)F]Fluoromethyl)-(+)-McN5652.Eur Neuropsychopharmacol2003,13:387-397.
[189]Kung MP,Stevenson DA,Plssl K,Meegalla SK,Beckwith A,Essman WD,et al.[~(99m)Tc]TRODAT-1:a novel technetium-99m complex as a dopamine transporter imaging agent.European J Nucl Med 1997,24:372-380.
[190]Kung HF,Kung MP,Wey SP,Lin KJ,Yen TC.Clinical acceptance of a molecular imaging agent:a long march with[Tc-99m]TRODAT.Nucl Med Biol 2007,34:787-789.
[191]Tan PZ,Baldwin RM,Van Dyck CH,Al-Tikriti M,Roth B,Khan N,et al.Characterization of radioactive metabolites of 5-HT_(2A)receptor PET ligand[~(18)F]altanserin in human and rodent.Nucl Med Biol 1999,26:601-608.
[192]van Dyck CH,Tan PZ,Baldwin RM,Amici LA,Garg PK,Ng CK,et al.PET quantification of 5-HT_(2A)receptors in the human brain:a constant infusion paradigm with[~(18)F]altanserin.J Nucl Med 2000,41:234-241.
[193]Liptrot M,Adams KH,Martiny L,Pinborg LH,Lonsdale MN,Olsen NV,et al.Cluster analysis in kinetic modelling of the brain:a noninvasive alternative to arterial sampling.Neuroimage 2004,21:483-493.
[194]Bergstrom KA,Halldin C,Kuikka JT,Swahn CG,Tiihonen J,Hiltunen J,et al.Lipophilic metabolite of[~(123)I]β-CIT in human plasma may obstruct quantitation of the dopamine transporter.Synapse 1995,19:297-300.
[195]Lundkvist C,Halldin C,Swahn CG,Ginovart N,Farde L.Different brain radioactivity curves in a PET study with[~(11)C]B-CIT labelled in two different positions.Nucl Med Biol 1999,26:343-350.
[196]Zoghbi SS,Shetty HU,Ichise M,Fujita M,Imaizumi M,Liow JS,et al.PET imaging of the dopamine transporter with~(18)F-FECNT:a polar radiometabolite confounds brain radioligand measurements.J Nucl Med 2006,47:520-527.
[197]Shetty HU,Zoghbi SS,Liow JS,Ichise M,Hong J,Musachio JL,ef at.Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand[~(11)C]PE2I.Eur J Nucl Med Mol Imaging 2007,34:667-678.
[198]Peyronneau MA,Saba W,Dolle F,Goutal S,Coulon C,Bottlaender M,et al.Difficulties in dopamine transporter radioligand PET analysis:the example of LBT-999 using[~(18)F]and[~(11)C]labelling:part II:Metabolism studies.Nucl Med Biol2012,39:347-359.
[199]Bergstr6m KA,Halldin C,Hall H,Lundkvist C,Ginovart N,Swahn CG,et al.In vitro and in vivo characterisation of norB-CIT:a potential radioligand for visualisation of the serotonin transporter in the brain.European J Nucl Med 1997,24:596-601.
[200]Guengerich FP.Common and uncommon cytochrome P450reactions related to metabolism and chemical toxicity.Chem Res Toxicol 2001,14:611-650.
[201]Carroll Fl,Blough BE,Nie Z,Kuhar MJ,Howell LL,Navarro HA.Synthesis and monoamine transporter binding properties of 3beta-(3',4'-disubstituted phenyl)tropane-2beta-carboxylic acid methyl esters.J Med Chem 2005,48:2767-2771.
[202]Mori T,Sun LQ,Kobayashi M,Kiyono Y,Okazawa H,Furukawa T,et al.Preparation and evaluation of ethyl[~(18)F]fluoroacetate as a proradiotracer of[~(18)F]fluoroacetate for the measurement of glial metabolism by PET.Nucl Med Biol2009,36:155-162.
[203]Dienel GA,Popp D,Drew PD,Ball K,Krisht A,Cruz NF.Preferential labeling of glial and meningial brain tumors with[2-~(14)C]acetate.J Nucl Med 2001,42:1243-1250.
[204]Lear JL,Ackermann RF.Evaluation of radiolabeled acetate and fluoroacetate as potential tracers of cerebral oxidative metabolism.Metab Brain Dis 1990,5:45-56.
[205]Davson H,Segal MB.Physiology of the CSF and Blood-Brain Barriers.Boca Raton,USA:CRC Press,1996.
[206]Rogers GA,Stone-Elander S,Ingvar M,Eriksson L,Parsons SM,Widen L.~(18)F-labeiled vesamicol derivatives:syntheses and preliminary in vivo small animal positron emission tomography evaluation.Nucl Med Biol 1994,21:219-230.
[207]Tu LQ,Wright PF,Rix CJ,Ahokas JT.Is fluoroacetatespecific defluorinase a glutathione S-transferase?Comp Biochem Physiol C Toxicol Pharmacol 2006,143:59-66.
[208]Johnson JA,el Barbary A,Kornguth SE,Brugge JF,Siegel FL.Glutathione S-transferase isoenzymes in rat brain neurons and glia.J Neurosci 1993,13:2013-2023.
[209]Brust P,Hinz R,Kuwabara H,Hesse S,Zessin J,Pawelke B,et al.In vivo measurement of the serotonin transporter with(S)-([~(18)F]fluoromethyl)-(+)-McN5652.Neuropsychopharmacology 2003,28:2010-2019.
[210]Hesse S,Brust P,Mading P,Becker GA,Patt M,Seese A,et al.Imaging of the brain serotonin transporters(SERT)with~(18)F-labelled fluoromethyl-McN5652 and PET in humans.Eur J Nucl Med Mol Imaging 2012,39:1001-1011.
[211]Szabo Z,Scheffel U,Mathews WB,Ravert HT,Szabo K,Kraut M,et al.Kinetic analysis of[~(11)C]McN5652:a serotonin transporter radioligand.J Cereb Blood Flow Metab 1999,19:967-981.
[212]Brust P,Patt JT,Deuther-Conrad W,Becker G,Patt M,Schildan A,et al.In vivo measurement of nicotinic acetylcholine receptors with[~(18)F]norchloro-fluoro-homoepibatidine.Synapse 2008,62:205-218.
[213]Patt M,Becker GA,Grossmann U,Habermann B,Schildan A,Wilke S,et al.Evaluation of metabolism,plasma protein binding and other biological parameters after administration of(-)-[~(18)F]flubatine in humans.Nucl Med Biol 2014.doi.org/10.1016/j.nucmedbio.2014.1003.1018.
[214]Becker GA,Wilke S,Schonknecht P,Patt M,Luthardt J,Hesse S,et al.Comparison of(-)-[~(18)F]-flubatine and 2-[~(18)F]FA-85380 binding to nicotinic alpha4beta2 acetylcholine receptors in human brains.Eur J Nucl Med Mol Imaging2013,40(Suppl.2):S271.
[215]Fasinu P,Bouic PJ,Rosenkranz B.Liver-based in vitro technologies for drug biotransformation studies-a review.Curr Drug Metab 2012,13:215-224.
[216]Davydov DR.Microsomal monooxygenase as a multienzyme system:the role of P450-P450 interactions.Expert Opin Drug Metab Toxicol 2011,7:543-558.
[217]Stabin MG.Fundamentals of Nuclear Medicine Dosimetry.Springer,2008.
[218]van de Waterbeemd H,Camenisch G,Folkers G,Chretien JR,Raevsky OA.Estimation of blood-brain barrier crossing of drugs using molecular size and shape,and H-bonding descriptors.J Drug Target 1998,6:151-165.
[219]Ball K,Bouzom F,Scherrmann JM,Walther B,Decleves X.Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier-towards a mechanistic IVIVE-based approach.AAPS J 2013,15:913-932.
[220]Shawahna R,Decleves X,Scherrmann JM.Hurdles with using in vitro models to predict human blood-brain barrier drug permeability:a special focus on transporters and metabolizing enzymes.Curr Drug Metab 2013,14:120-136.
[221]Uchida Y,Ohtsuki S,Katsukura Y,Ikeda C,Suzuki T,Kamiie J,et al.Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors.J Neurochem2011,117:333-345.
[222]Rfitering S,Scheunemann M,Fischer S,Hiller A,Peters D,Deuther-Conrad W,et al.Radiosynthesis and first evaluation in mice of[~(18)F]NS14490 for molecular imaging of a7 nicotinic acetylcholine receptors.Bioorg Med Chem 2013,21:2635-2642.
[223]Syvanen S,Lindhe O,Palner M,Kornum BR,Rahman O,Langstr(o|¨)m B,et al.Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport.Drug Metab Dispos 2009,37:635-643.
[224]Wagner HN,Jr.,Burns HD,Dannals RF,Wong DF,Langstrom B,DuelferT,et al.Imaging dopamine receptors in the human brain by positron tomography.Science 1983,221:1264-1266.
[225]Ehrin E,Farde L,de Paulis T,Eriksson L,Greitz T,Johnstr(o|¨)m P,et al.Preparation of~(11)C-labelled Raclopride,a new potent dopamine receptor antagonist:preliminary PET studies of cerebral dopamine receptors in the monkey.Int J Appl Radiat Isot 1985,36:269-273.
[226]Chan GL,Holden JE,Stoessl AJ,Doudet DJ,Wang Y,Dobko T,et al.Reproducibility of the distribution of carbon-11-SCH23390,a dopamine D,receptor tracer,in normal subjects.J Nucl Med 1998,39:792-797.
[227]Parsey RV,Arango V,Olvet DM,Oquendo MA,Van Heertum RL,John Mann J.Regional heterogeneity of 5-HT_(1A)receptors in human cerebellum as assessed by positron emission tomography.J Cereb Blood Flow Metab 2005,25:785-793.
[228]Biver F,Goldman S,Luxen A,Monclus M,Forestini M,Mendlewicz J,et al.Multicompartmental study of F-18altanserin binding to brain 5HT_2 receptors in humans using positron emission tomography.Eur J Nucl Med 1994,21:937-946.
[229]Itoh T,Tanaka M,Kobayashi K,Suzuki K,Inoue O.Binding kinetics of~(11)C-N-methyl piperidyl benzilate(~(11)C-NMPB)in a rhesus monkey brain using the cerebellum as a reference region.Ann Nucl Med 2005,19:499-505.
[230]Deuther-Conrad W,Fischer S,Hiller A,Becker G,Cumming P,Xiong G,et al.Assessment ofα7 nicotinic acetylcholine receptor availability in porcine brain with[~(18)F]NS10743.Eur J Nucl Med Mol Imaging 2011,38:1541-1549.
[231]Flesher JE,Scheffel U,London ED,Frost JJ.In vivo labeling of nicotinic cholinergic receptors in brain with[3H]cytisine.Life Sci 1994,54:1883-1890.
[232]Ishiwata K,Kawamura K,Wang WF,Tsukada H,Harada N,Mochizuki H,et al.Evaluation of in vivo selective binding of[~(11)C]doxepin to histamine H,receptors in five animal species.Nucl Med Biol 2004,31:493-502.
[233]Kish SJ,Furukawa Y,Chang LJ,Tong J,Ginovart N,Wilson A,et al.Regional distribution of serotonin transporter protein in postmortem human brain:Is the cerebellum a SERT-free brain region?Nucl Med Biol 2005,32:123-128.
[234]Brust P,Hesse S,Müller U,Szabo Z.Neuroimaging of the serotonin transporter-possibilities and pitfalls.Curr Psychiat Rev 2006,2:111-149.
[235]Marjamaki P,Zessin J,Eskola O,Gronroos T,Haaparanta M,Bergman J,et al.S-[~(18)F]fluoromethyl-(+)-McN5652,a PET tracer for the serotonin transporter:Evaluation in rats.Synapse 2003,47:45-53.
[236]Deuther-Conrad W,Maisonial A,Patt M,Stittsworth S,Becker G,Habermann B,et al.Discovery of enantioselective suitability of(R)-(+)-and(S)-(-)-[~(18)F]fluspidine forσ_1 receptor imaging.J Label Comp Radiopharm 2013,56:S55.
[237]Brust P,Deuther-Conrad W,Becker G,Patt M,Donat CK,Stittsworth S,et al.Distinctive in vivo kinetics of the new sigmal receptor ligands(R)-(+)-and(S)-(-)-~(18)F-fluspidine in porcine brain.J Nucl Med 2014,pii:jnumed.114.137562.
[238]Leenders KL,Gibbs JM,Frackowiak RS,Lammertsma AA,Jones T.Positron emission tomography of the brain:new possibilities for the investigation of human cerebral pathophysiology.Prog Neurobiol 1984,23:1-38.
[239]Mintun MA,Raichle ME,Kilbourn MR,Wooten GF,Welch MJ.A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.Ann Neurol1984,15:217-227.
[240]Miyoshi S,Mitsuoka K,Nishimura S,Veltkamp SA.Radioisotopes in Drug Research and Development:Focus on Positron Emission Tomography.In:Singh N(Ed).Radioisotopes-Applications in Bio-Medical Science.InTech,2011:93-113.
[241]Yanai K,Ido T,Ishiwata K,Hatazawa J,Watanuki S,Takahashi T,et al.Characteristics of specific in vivo labeling of neuroleptic binding sites with 3-N-[~(11)C]methylspiperone.European J Nucl Med 1986,11:438-443.
[242]Brust P,Shaya EK,Jeffries KJ,Dannals RF,Ravert HT,Wilson AA,et al.Effects of vasopressin on blood-brain transfer of methionine in dogs.J Neurochem 1992,59:1421-1429.
[243]Kong FL,Ford RJ,Yang DJ.Managing lymphoma with nonFDG radiotracers:current clinical and preclinical applications.Biomed Res Int 2013,2013:626910.
[244]Prenen GH,Go KG,Paans AM,Zuiderveen F,Vaalburg W,Kamman RL,et al.Positron emission tomographical studies of 1-~(11)C-acetoacetate,2-~(18)F-fluoro-deoxy-D-glucose,and L-1-~(11)C-tyrosine uptake by cat brain with an experimental lesion.Acta Neurochirurgica 1989,99:166-172.
[245]Ginovart N,Wilson AA,Meyer JH,Hussey D,Houle S.[~(11)C]-DASB,a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter:PET characterization and evaluation in cats.Synapse 2003,47:123-133.
[246]Bauer R,Bergmann R,Beyer GJ,Manfrass P,Steinbach J,Kretzschmar M,et al.Investigations of cerebral glucose utilization into the newborn brain:a[~(18)F]-FDG positron emission tomography study using a high resolution multiwire proportional chamber detector device.Exp Pathol 1991,42:229-233.
[247]Sauleau P,Lapouble E,Val-Laillet D,Malbert CH.The pig model in brain imaging and neurosurgery.Animal 2009,3:1138-1151.
[248]Alstrup AKO,Smith DF.PET neuroimaging in pigs.Scand J Lab Anim Sci 2012,39:25-45.
[249]Herzog H.PET/MRI:challenges,solutions and perspectives.Z Med Phys 2012,22:281-298.
[250]Herzog H,van den Hoff J.Combined PET/MR systems:an overview and comparison of currently available options.Q J Nucl Med Mol Imaging 2012,56:247-267.
[251]Xi W,Tian M,Zhang H.Molecular imaging in neuroscience research with small-animal PET in rodents.Neurosci Res2011,doi:10.1016/j.neures.2010.12.017.
[252]Lancelot S,Zimmer L.Small-animal positron emission tomography as a tool for neuropharmacology.Trends Pharmacol Sci 2010,31:411-417.
[253]Syvanen S,Labots M,Tagawa Y,Eriksson J,Windhorst AD,Lammertsma AA,et al.Altered GABA_A receptor density and unaltered blood-brain barrier transport in a kainate model of epilepsy:an in vivo study using~(11)C-flumazenil and PET.J Nucl Med 2012,53:1974-1983.
[254]Gunn RN,Gunn SR,Turkheimer FE,Aston JA,Cunningham VJ.Positron emission tomography compartmental models:a basis pursuit strategy for kinetic modeling.J Cereb Blood Flow Metab 2002,22:1425-1439.
[255]Schmidt KC,Turkheimer FE.Kinetic modeling in positron emission tomography.Quarterly J Nucl Med 2002,46:70-85.
[256]Laruelle M,Slifstein M,Huang Y.Positron emission tomography:imaging and quantification of neurotransporter availability.Methods 2002,27:287-299.
[257]Watabe H,Ikoma Y,Kimura Y,Naganawa M,Shidahara M.PET kinetic analysis-compartmental model.Ann Nucl Med2006,20:583-588.
[258]van den Hoff J.Principles of quantitative positron emission tomography.Amino Acids 2005,29:341-353.
[259]van den Hoff J.Kinetic Modelling.In:Kiessling F,Pichler BJ.Small Animal Imaging:Basics and Practical Guide.Springer,2010:387-404.
[260]Brust P,Zessin J,Kuwabara H,Pawelke B,Kretzschmar M,Hinz R,et al.Positron emission tomography imaging of the serotonin transporter in the pig brain using[~(11)C](+)-McN5652and S-([~(18)F]fluoromethyl)-(+)-McN5652.Synapse 2003,47:143-151.
[261]Lammertsma AA,Bench CJ,Hume SP,Osman S,Gunn K,Brooks DJ,et al.Comparison of methods for analysis of clinical C-11 raclopride studies.J Cereb Blood Flow Metab1996,16:42-52.
[262]Lammertsma AA,Hume SP.Simplified reference tissue model for PET receptor studies.Neuroimage 1996,4:153-158.
[263]Wang G,Qi J.Direct estimation of kinetic parametric images for dynamic PET.Theranostics 2013,3:802-815.
[264]Patlak CS,Blasberg RG,Fenstermacher JD.Graphical evaluation of blood-to-brain transfer constants from multipletime uptake data.J Cereb Blood Flow Metab 1983,3:1-7.
[265]Patlak CS,Blasberg RG.Graphical evaluation of bloodto-brain transfer constants from multiple-time uptake data.Generalizations.J Cereb Blood Flow Metab 1985,5:584-590.
[266]Gjedde A.High-and low-affinity transport of D-glucose from blood to brain.J Neurochem 1981,36:1463-1471.
[267]Logan J,Fowler JS,Volkow ND,Wolf AP,Dewey SL,Schlyer DJ,et al.Graphical analysis of reversible radioligand binding from time-activity measurements applied to[N-~(11)C-methyl]-(-)-cocaine PET studies in human subjects.J Cereb Blood Flow Metab 1990,10:740-747.
[268]Wang JZ,Qiu P,Liu RKJ,Szabo Z.Model-Based receptor quantization analysis for PET parametric imaging.Conf Proc IEEE Eng Med Biol Soc 2005,6:5908-5911.
[269]Dennan S,Decristoforo Ce.The Radiopharmacy.A Technologist's Guide.European Association of Nuclear Medicine,2008.
[270]Elsinga P,Todde S,Penuelas I,Meyer G,Farstad B,FaivreChauvet A,et al.Guidance on current good radiopharmacy practice(cGRPP)for the small-scale preparation of radiopharmaceuticals.Eur J Nucl Med Mol Imaging 2010,37:1049-1062.
[271]Verbruggen A,Coenen HH,Deverre JR,Guilloteau D,Langstrom B,Salvadori PA,et al.Guideline to regulations for radiopharmaceuticals in early phase clinical trials in the EU.Eur J Nucl Med Mol Imaging 2008,35:2144-2151.
[272]Zessin J,Eskola O,Steinbach J,Bergman J,Marjamaki P,Brust P,et al.Synthesis and first biological evaluation of the[~(18)F]fluormethyl-analog of(+)-MCN5652,a tracer for imaging the serotonin transporter.Nuklearmedizin 2000,39:A36.[Article in German language]
[273]Petrou M,Koeppe R,Scott P,Bohnen N,Kilbourn M,Frey K.PET imaging of the vesicular acetylcholine transporter.J Nucl Med 2012,53(Supplement 1):290.
[274]Farde L,Ehrin E,Eriksson L,Greitz T,Hall H,Hedstrom CG,et a/.Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.Proc Natl Acad Sci U S A 1985,82:3863-3867.
[275]Maziere M,Hantraye P,Prenant C,Sastre J,Comar D.Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[~(11)C]methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate(RO15.1788-~(11)C):a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.Int J Appl Radiat Isot 1984,35:973-976.
[276]Rowland DJ,Cherry SR.Small-animal preclinical nuclear medicine instrumentation and methodology.Semin Nucl Med2008,38:209-222.
[2]Pichler BJ,Judenhofer MS,Pfannenberg C.Multimodal imaging approaches:PET/CT and PET/MRI.Handb Exp Pharmacol 2008:109-132.
[3]Drzezga A,Barthel H,Minoshima S,Sabri O.Potential clinical applications of PET/MR imaging in neurodegenerative diseases.J Nucl Med 2014,55:1-9.
[4]Levi H.George von Hevesy memorial lecture.George Hevesy and his concept of radioactive indicators—in retrospect.Eur J Nucl Med 1976,1:3-10.
[5]Sampson CD(Ed.).Textbook of Radiopharmacy:Theory and Practice.3rd.ed.Amsterdam:Gordan and Breach Science Publishers,1999.
[6]Brust P,Deuther-Conrad W,Donat CK,Barthel H,Riss P,Paterson L,et al.Preclinical aspects of nicotinic acetylcholine receptor imaging.In:Dierckx RAJ,Otte A,de Vries EFJ,et al.(Eds.).PET and SPECT of Neurobiological Systems.Springer,2014:465-512.
[7]Virdee K,Cumming P,Caprioli D,Jupp B,Rominger A,Aigbirhio Fl,et al.Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders.Neurosci Biobehav Rev 2012,36:1188-1216.
[8]Melhem M.Translation of central nervous system occupancy from animal models:application of pharmacokinetic/pharmacodynamic modeling.J Pharmacol Exp Ther 2013,347:2-6.
[9]Frey KA,Koeppe RA,Mulholland GK,Jewett D,Hichwa R,Ehrenkaufer RL,et al.In vivo muscarinic cholinergic receptor imaging in human brain with[~(11)C]scopolamine and positron emission tomography.J Cereb Blood Flow Metab 1992,12:147-154.
[10]Xie G,Gunn RN,Dagher A,Daloze T,Plourde G,Backman SB,et al.PET quantification of muscarinic cholinergic receptors with[N-11C-methyl]-benztropine and application to studies of propofol-induced unconsciousness in healthy human volunteers.Synapse 2004,51:91-101.
[11]Yamamoto S,Ouchi Y,Nakatsuka D,Tahara T,Mizuno K,Tajima S,et al.Reduction of[~(11)C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.PLoS One 2012,7:e51515.
[12]Ichise M,Cohen RM,Carson RE.Noninvasive estimation of normalized distribution volume:application to the muscarinic-2 ligand[~(18)F]FP-TZTP.J Cereb Blood Flow Metab2008,28:420-430.
[13]Sabri O,Kendziorra K,Wolf H,Gertz HJ,Brust P.Acetylcholine receptors in dementia and mild cognitive impairment.Eur J Nucl Med Mol Imaging 2008,35 Suppl 1:S30-45.
[14]Ding YS,Fowler JS,Logan J,Wang GJ,Telang F,Garza V,et al.6-[~(18)F]Fluoro-A-85380,a new PET tracer for the nicotinic acetylcholine receptor:studies in the human brain and in vivo demonstration of specific binding in white matter.Synapse 2004,53:184-189.
[15]Wong DF,Kuwabara H,Kim J,Brasic JR,Chamroonrat W,Gao Y,et al.PET imaging of high-affinityα_4β_2 nicotinic acetylcholine receptors in humans with 18F-AZAN,a radioligand with optimal brain kinetics.J Nucl Med 2013,54:1308-1314.
[16]Sabri O,Wilke S,Graf S,Schonknecht P,Becker G,Patt M,et al.Cerebralα_4β_2 nicotinic acetylcholine receptors(nAChRs)in early Alzheimer disease(AD)assessed with the new PET tracer(-)-[~(18)F]-norchloro-fluoro-homoepibatidine(NCFHEB).J Nucl Med 2011,52(Suppl.1):1267.
[17]Toyohara J,Sakata M,Wu J,Ishikawa M,Oda K,Ishii K,et al.Preclinical and the first clinical studies on[~(11)C]CHIBA-1001 for mapping a7 nicotinic receptors by positron emission tomography.Ann Nucl Med 2009,23:301-309.
[18]Bauer A,Holschbach MH,Meyer PT,Boy C,Herzog H,Olsson RA,et al.In vivo imaging of adenosine A,receptors in the human brain with[~(18)F]CPFPX and positron emission tomography.Neuroimage 2003,19:1760-1769.
[19]Fukumitsu N,Ishii K,Kimura Y,Oda K,Hashimoto M,Suzuki M,et al.Adenosine A,receptors using 8-dicyclopropylmethyl-1-[~(11)C]methyl-3-propylxanthine PET in Alzheimer's disease.Ann Nucl Med 2008,22:841-847.
[20]Mishina M,Ishiwata K,Naganawa M,Kimura Y,Kitamura S,Suzuki M,et al.Adenosine A_(2A)receptors measured with[~(11)C]TMSX PET in the striata of Parkinson's disease patients.PLoS One 2011,6:e17338.
[21]Ramlackhansingh AF,Bose SK,Ahmed I,Turkheimer FE,Pavese N,Brooks DJ.Adenosine 2_A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease.Neurology 2011,76:1811-1816.
[22]Burns HD,Van Laere K,Sanabria-Bohorquez S,Hamill TG,Bormans G,Eng WS,et al.[~(18)F]MK-9470,a positron emission tomography(PET)tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor.Proc Natl Acad Sci U S A 2007,104:9800-9805.
[23]Terry GE,Hirvonen J,Liow JS,Seneca N,Tauscher JT,Schaus JM,et al.Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography.Eur J Nucl Med Mol Imaging 2010,37:1499-1506.
[24]Wong DF,Kuwabara H,Horti AG,Raymont V,Brasic J,Guevara M,et al.Quantification of cerebral cannabinoid receptors subtype 1(CB1)in healthy subjects and schizophrenia by the novel PET radioligand[~(11)C]OMAR.Neuroimage 2010,52:1505-1513.
[25]Ahmad R,Koole M,Evens N,Serdons K,Verbruggen A,Bormans G,et al.Whole-body biodistribution and radiation dosimetry of the cannabinoid type 2 receptor ligand[~(11)C]-NE40 in healthy subjects.Mol Imaging Biol 2013.
[26]Farde L,Halldin C,Stone-Elander S,Sedvall G.PET analysis of human dopamine receptor subtypes using~(11)C-SCH 23390and~(11)C-raclopride.Psychopharmacology 1987,92:278-284.
[27]Karlsson P,Farde L,Halldin C,Swahn CG,Sedvall G,Foged C,et al.PET examination of[~(11)C]NNC 687 and[~(11)C]NNC 756 as new radioligands for the D,-dopamine receptor.Psychopharmacology 1993,113:149-156.
[28]Slifstein M,Kolachana B,Simpson EH,Tabares P,Cheng B,Duvall M,et al.COMT genotype predicts cortical-limbic D,receptor availability measured with[~(11)C]NNC112 and PET.Mol Psychiatry 2008,13:821-827.
[29]Farde L,Hall H,Ehrin E,Sedvall G.Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET.Science 1986,231:258-261.
[30]Wong DF,Wagner HN,Jr.,Tune LE,Dannals RF,Pearlson GD,Links JM,et al.Positron emission tomography reveals elevated D_2 dopamine receptors in drug-naive schizophrenics.Science 1986,234:1558-1563.
[31]Narendran R,Frankle WG,Mason NS,Laymon CM,Lopresti BJ,Price JC,et al.Positron emission tomography imaging of D~_(2/3)agonist binding in healthy human subjects with the radiotracer[~(11)C]-N-propyl-norapomorphine:preliminary evaluation and reproducibility studies.Synapse 2009,63:574-584.
[32]Otsuka T,Ito H,Halldin C,Takahashi H,Takano H,Arakawa R,et al.Quantitative PET analysis of the dopamine D_2 receptor agonist radioligand~(11)C-(R)-2-CH30-N-npropylnorapomorphine in the human brain.J Nucl Med 2009,50:703-710.
[33]Farde L,Suhara T,Nyberg S,Karlsson P,Nakashima Y,Hietala J,et al.A PET-study of[~(11)C]FLB 457 binding to extrastriatal D_2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients.Psychopharmacology1997,133:396-404.
[34]Mukherjee J,Christian BT,Dunigan KA,Shi B,Narayanan TK,Satter M,et al.Brain imaging of~(18)F-fallypride in normal volunteers:blood analysis,distribution,test-retest studies,and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors.Synapse 2002,46:170-188.
[35]Ginovart N,Willeit M,Rusjan P,Graff A,Bloomfield PM,Houle S,et al.Positron emission tomography quantification of[~(11)C]-(+)-PHNO binding in the human brain.J Cereb Blood Flow Metab 2007,27:857-871.
[36]Moresco RM,Scheithauer BW,Lucignani G,Lombardi D,Rocca A,Losa M,et al.Oestrogen receptors in meningiomas:a correlative PET and immunohistochemical study.Nucl Med Comm1997,18:606-615.
[37]Toyohara J,Sakata M,Fujinaga M,Yamasaki T,Oda K,Ishii K,et al.Preclinical and the first clinical studies on[~(11)C]ITMM for mapping metabotropic glutamate receptor subtype1 by positron emission tomography.Nucl Med Biol 2013,40:214-220.
[38]Ametamey SM,Treyer V,Streffer J,Wyss MT,Schmidt M,Blagoev M,et al.Human PET studies of metabotropic glutamate receptor subtype 5 with~(11)C-ABP688.J Nucl Med2007,48:247-252.
[39]Brown AK,Kimura Y,Zoghbi SS,Simeon FG,Liow JS,Kreisl WC,et al.Metabotropic glutamate subtype 5 receptors are quantified in the human brain with a novel radioligand for PET.J Nucl Med 2008,49:2042-2048.
[40]Kagedal M,Cselenyi Z,Nyberg S,Jonsson S,Raboisson P,Stenkrona P,et al.Non-linear mixed effects modelling of positron emission tomography data for simultaneous estimation of radioligand kinetics and occupancy in healthy volunteers.Neuroimage 2012,61:849-856.
[41]Wong DF,Waterhouse R,Kuwabara H,Kim J,Brasic JR,Chamroonrat W,et al.~(18)F-FPEB,a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors:a firstin-human study of radiochemical safety,biokinetics,and radiation dosimetry.J Nucl Med 2013,54:388-396.
[42]Kumlien E,Hartvig P,Valind S,Oye I,Tedroff J,Langstrdm B.NMDA-receptor activity visualized with(S)-[N-methyl-~(11)C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy.Epilepsia 1999,40:30-37.
[43]Hammers A,Asselin M,Brooks DJ,Luthra SK,Hume SP,Thompson PJ,et al.Correlation of memory function with binding of[C-11]CNS 5161,a novel putative NMDA ion channel PET ligand.Neuroimage 2004,22(Suppl 2):T54-55.
[44]Ametamey SM,Bruehlmeier M,Kneifel S,Kokic M,Honer M,Arigoni M,et al.PET studies of~(18)F-memantine in healthy volunteers.Nucl Med Biol 2002,29:227-231.
[45]McGinnity CJ,Hammers A,Riano Barros DA,Luthra SK,Jones PA,Trigg W,et al.Initial evaluation of~(18)F-GE-179,a putative PET Tracer for activated N-methyl D-aspartate receptors.J Nucl Med 2014,55:423-430.
[46]Matsumoto R,Haradahira T,Ito H,Fujimura Y,Seki C,Ikoma Y,et al.Measurement of glycine binding site of N-methylD-asparate receptors in living human brain using 4-acetoxy derivative of L-703,717,4-acetoxy-7-chloro-3-[3-(4-[~(11)C]methoxybenzyl)phenyl]-2(1H)-quinolone(AcL703)with positron emission tomography.Synapse 2007,61:795-800.
[47]Yanai K,Watanabe T,Itoh M,Hatazawa J,Iwata R,Ido T.Labeling of histamine H1-receptors in vivo:a compartment model analysis and positron emission tomographic imaging.Agents Actions Suppl 1991,33:381-386.
[48]Ashworth S,Rabiner EA,Gunn RN,Plisson C,Wilson AA,Comley RA,et al.Evaluation of~(11)C-GSK189254 as a novel radioligand for the H3 receptor in humans using PET.J Nucl Med 2010,51:1021-1029.
[49]Persson A,Ehrin E,Eriksson L,Farde L,Hedstr(o|¨)m CG,Litton JE,et al.Imaging of[~(11)C]-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography.J Psychiatric Res 1985,19:609-622.
[50]Leveque P,Sanabria-Bohorquez S,Bol A,De Voider A,Labar D,Van Rijckevorsel K,et al.Quantification of human brain benzodiazepine receptors using[~(18)F]fluoroethylflumazenil:a first report in volunteers and epileptic patients.Eur J Nucl Med Mol Imaging 2003,30:1630-1636.
[51]Lee JD,Park HJ,Park ES,Kim DG,Rha DW,Kim EY,et al.Assessment of regional GABA_A receptor binding using~(18)F-fluoroflumazenil positron emission tomography in spastic type cerebral palsy.Neuroimage 2007,34:19-25.
[52]Massaweh G,Schirrmacher E,la Fougere C,Kovacevic M,Wangler C,Jolly D,et al.Improved work-up procedure for the production of[~(18)F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke.Nucl Med Biol 2009,36:721-727.
[53]Lingford-Hughes A,Hume SP,Feeney A,Hirani E,Osman S,Cunningham VJ,et al.Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with[~(11)C]Ro15 4513 positron emission tomography.J Cereb Blood Flow Metab 2002,22:878-889.
[54]Frost JJ,Mayberg HS,Sadzot B,Dannals RF,Lever JR,Ravert HT,et al.Comparison of[~(11)C]diprenorphine and[~(11)C]carfentanil binding to opiate receptors in humans by positron emission tomography.J Cereb Blood Flow Metab 1990,10:484-492.
[55]Madar I,Lesser RP,Krauss G,Zubieta JK,Lever JR,Kinter CM,et al.Imaging of a-and u-opioid receptors in temporal lobe epilepsy by positron emission tomography.Ann Neurol1997,41:358-367.
[56]Tomasi G,Zheng M-Q,Weinzimmer D,Lin S-F,Nabulsi N,Williams W,et al.Kinetic modeling of the kappa agonist tracer[~(11)C]GR103545 in humans.J Nucl Med 2010,51(Supplement 2):1293.
[57]Cohen RM,Carson RE,Sunderland T.Opiate receptor avidity in the thalamus is sexually dimorphic in the elderly.Synapse2000,38:226-229.
[58]Baumgartner U,Buchholz HG,Bellosevich A,Magerl W,Siessmeier T,Rolke R,et al.High opiate receptor binding potential in the human lateral pain system.Neuroimage2006,30:692-699.
[59]Hostetler ED,Sanabria-Bohorquez S,Fan H,Zeng Z,Gantert L,Williams M,et al.Synthesis,characterization,and monkey positron emission tomography(PET)studies of[~(18)F]Y1-973,a PET tracer for the neuropeptide Y Y,receptor.Neuroimage2011,54:2635-2642.
[60]Pike VW,McCarron JA,Lammerstma AA,Hume SP,Poole K,Grasby PM,et al.First delineation of 5-HT_(1A)receptors in human brain with PET and"C WAY-100635.Eur J Pharmacol 1995,283:R1-3.
[61]Parsey RV,Slifstein M,Hwang DR,Abi-Dargham A,Simpson N,Mawlawi O,et al.Validation and reproducibility of measurement of 5-HT_(1A)receptor parameters with[carbonyl-~(11)C]WAY-100635 in humans:comparison of arterial and reference tisssue input functions.J Cereb Blood Flow Metab2000,20:1111-1133.
[62]Andree B,Halldin C,Pike VW,Gunn RN,Olsson H,Farde L.The PET radioligand[carbonyl-~(11)C]desmethyl-WAY-100635binds to 5-HT_(1A)receptors and provides a higher radioactive signal than[carbonyl-~(11)C]WAY-100635 in the human brain.J Nucl Med 2002,43:292-303.
[63]Houle S,Wilson AA,Inaba T,Fisher N,DaSilva JN.Imaging5-HT_(1A)receptors with positron emission tomography:initial human studies with[~(11)C]CPC-222.Nucl Med Comm 1997,18:1130-1134.
[64]Milak MS,DeLorenzo C,Zanderigo F,Prabhakaran J,Kumar JS,Majo VJ,et al.In vivo quantification of human serotonin1A receptor using~(11)C-CUMI-101,an agonist PET radiotracer.J Nucl Med 2010,51:1892-1900.
[65]Costes N,Merlet I,Zimmer L,Lavenne F,Cinotti L,Delforge J,et al.Modeling[~(18)F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine_(1A)receptor concentration with multiinjection.J Cereb Blood Flow Metab 2002,22:753-765.
[66]Theodore WH,Giovacchini G,Bonwetsch R,Bagic A,Reeves-Tyer P,Herscovitch P,et al.The effect of antiepileptic drugs on 5-HT-receptor binding measured by positron emission tomography.Epilepsia 2006,47:499-503.
[67]Gallezot JD,Nabulsi N,Neumeister A,Planeta-Wilson B,Williams WA,Singhal T,et al.Kinetic modeling of the serotonin 5-HT_(1BN)receptor radioligand[~(11)C]P943 in humans.J Cereb Blood Flow Metab 2010,30:196-210.
[68]Varnas K,Nyberg S,Halldin C,Varrone A,Takano A,Karlsson P,et al.Quantitative analysis of[~(11)C]AZ10419369binding to 5-HT_(1B)receptors in human brain.J Cereb Blood Flow Metab 2011,31:113-123.
[69]Murrough JW,Henry S,Hu J,Gallezot JD,Planeta-Wilson B,Neumaier JF,et al.Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.Psychopharmacology 2011,213:547-553.
[70]Hinz R,Bhagwagar Z,Cowen PJ,Cunningham VJ,Grasby PM.Validation of a tracer kinetic model for the quantification of 5-HT_(2A)receptors in human brain with[~(11)C]MDL 100,907.J Cereb Blood Flow Metab 2007,27:161-172.
[71]Rosier A,Dupont P,Peuskens J,Bormans G,Vandenberghe R,Maes M,et al.Visualisation of loss of 5-HT_(2A)receptors with age in healthy volunteers using[~(18)F]altanserin and positron emission tomographic imaging.Psychiatry Res1996,68:11-22.
[72]van Dyck CH,Soares JC,Tan PZ,Staley JK,Baldwin RM,Amici LA,et al.Equilibrium modeling of 5-HT_(2A)receptors with[~(18)F]deuteroaltanserin and PET:feasibility of a constant infusion paradigm.Nucl Med Biol 2000,27:715-722.
[73]Trichard C,Paillere-Martinot ML,Attar-Levy D,Recassens C,Monnet F,Martinot JL.Binding of antipsychotic drugs to cortical 5-HT_(2A)receptors:a PET study of chlorpromazine,clozapine,and amisulpride in schizophrenic patients.Am J Psychiatry 1998,155:505-508.
[74]Ettrup A,da Cunha-Bang S,McMahon B,Lehel S,Dyssegaard A,Skibsted AW,et al.Serotonin 2_A receptor agonist binding in the human brain with[~(11)C]Cimbi-36.J Cereb Blood Flow Metab 2014.
[75]Marner L,Gillings N,Comley RA,Baare WF,Rabiner EA,Wilson AA,et al.Kinetic modeling of~(11)C-SB207145 binding to 5-HT_4 receptors in the human brain in vivo.J Nucl Med2009,50:900-908.
[76]Parker CA,Gunn RN,Rabiner EA,Slifstein M,Comley R,Salinas C,et al.Radiosynthesis and characterization of~(11)C-GSK215083 as a PET radioligand for the 5-HT_6 receptor.J Nucl Med 2012,53:295-303.
[77]Mishina M,Ishiwata K,Ishii K,Kitamura S,Kimura Y,Kawamura K,et al.Function of sigmal receptors in Parkinson's disease.Acta Neurol Scand 2005 112:103-107.
[78]Waterhouse RN,Nobler MS,Zhou Y,Chang RC,Morales O,Kuwabara H,et al.First evaluation of the sigmal receptor radioligand[~(18)F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine([~(18)F]FPS)in healthy humans.Neuroimage 2004,22:T29.
[79]Junck L,Olson JM,Ciliax BJ,Koeppe RA,Watkins GL,Jewett DM,et al.PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site.Ann Neurol1989,26:752-758.
[80]Banati RB,Goerres GW,Myers R,Gunn RN,Turkheimer FE,Kreutzberg GW,et al.[~(11)C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis.Neurology 1999,53:2199-2203.
[81]Brown AK,Fujita M,Fujimura Y,Liow JS,Stabin M,Ryu YH,et al.Radiation dosimetry and biodistribution in monkey and man of~(11)C-PBR28:a PET radioligand to image inflammation.J Nucl Med 2007,48:2072-2079.
[82]Endres CJ,Pomper MG,James M,Uzuner O,Hammoud DA,Watkins CC,et al.Initial evaluation of~(11)C-DPA-713,a novel TSPO PET ligand,in humans.J Nucl Med 2009,50:1276-1282.
[83]Yasuno F,Kosaka J,Ota M,Higuchi M,Ito H,Fujimura Y,et al.Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with[~(11)C]DAA1106.Psychiatry Res 2012,203:67-74.
[84]Gulyas B,Toth M,Schain M,Airaksinen A,Vas A,Kostulas K,et al.Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke:a PET study with the TSPO molecular imaging biomarker[~(11)C]vinpocetine.J Neurol Sci2012,320:110-117.
[85]Fujimura Y,Zoghbi SS,Simeon FG,Taku A,Pike VW,Innis RB,et al.Quantification of translocator protein(18 kDa)in the human brain with PET and a novel radioligand,F-18-PBR06.J Nucl Med 2009,50:1047-1053.
[86]Arlicot N,Vercouillie J,Ribeiro MJ,Tauber C,Venel Y,Baulieu JL,et al.Initial evaluation in healthy humans of[~(18)F]DPA-714,a potential PET biomarker for neuroinflammation.Nucl Med Biol 2012,39:570-578.
[87]Mizrahi R,Rusjan PM,Kennedy J,Pollock B,Mulsant B,Suridjan I,et al.Translocator protein(18 kDa)polymorphism(rs6971)explains in-vivo brain binding affinity of the PET radioligand[~(18)F]FEPPA.J Cereb Blood Flow Metab 2012,32:968-972.
[88]Guo Q,Colasanti A,Owen DR,Onega M,Kamalakaran A,Bennacef I,et al.Quantification of the specific translocator protein signal of~(18)F-PBR111 in healthy humans:a genetic polymorphism effect on in vivo binding.J Nucl Med 2013,54:1915-1923.
[89]Brust P,Deuther-Conrad W,Lehmkuhl K,Jia H,Wunsch B.Molecular imaging of a,receptors in vivo:current status and perspectives.Curr Med Chem 2014,21:35-69.
[90]Jansen KL,Faull RL,Storey P,Leslie RA.Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss.Brain Res 1993,623:299-302.
[91]Weissman AD,Casanova MF,Kleinman JE,London ED,De Souza EB.Selective loss of cerebral cortical sigma,but not PCP binding sites in schizophrenia.Biol Psychiatry 1991,29:41-54.
[92]van Waarde A,Rybczynska AA,Ramakrishnan N,Ishiwata K,Elsinga PH,Dierckx RA.Sigma receptors in oncology:therapeutic and diagnostic applications of sigma ligands.Curr Pharm Des 2010,16:3519-3537.
[93]Banister SD,Kassiou M.The therapeutic potential of sigma(a)receptors for the treatment of central nervous system diseases:evaluation of the evidence.Curr Pharm Des 2012,18:884-901.
[94]Megalizzi V,Le Mercier M,Decaestecker C.Sigma receptors and their ligands in cancer biology:overview and new perspectives for cancer therapy.Med Res Rev 2012,32:410-427.
[95]Schliebs R,Arendt T.The cholinergic system in aging and neuronal degeneration.Behav Brain Res 2011,221:555-563.
[96]Brust P,Deuther-Conrad W.Molecular imaging of a7nicotinic acetylcholine receptors in vivo:current status and perspectives.In:Bright P(Ed).Neuroimaging-Clinical Applications.InTech,2012:533-558.
[97]Brust P,Peters D,Deuther-Conrad W.Development of radioligands for the imaging ofα7 nicotinic acetylcholine receptors with positron emission tomography.Curr Drug Targets 2012,13:594-601.
[98]Kadir A,Almkvist O,Wall A,Langstrom B,Nordberg A.PET imaging of cortical~(11)C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease.Psychopharmacology 2006,188:509-520.
[99]Papke RL.Merging old and new perspectives on nicotinic acetylcholine receptors.Biochem Pharmacol 2014.doi:10.1016/j.bcp.2014.1001.1029.
[100]Moerlein SM.Molecular imaging and the development of new radiopharmaceuticals.In:Kowalsky RJ,Falen SW(Eds.).Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine.American Pharmacists Association(APhA),2011:741.
[101]Davenport AP,Russel FD.Radioligand Binding Assays:Theory and Practice.In:Mather SJ(Ed.).Current Directions in Radiopharmaceutical Research and Development.Kluwer Academic Publisher,1996:169-179.
[102]Koeppe RA.A panel discussion on the future of pharmacology and experimental tomography.In:Gjedde A,Hansen SB,Knudsen GM,Paulson OB(Eds.).Physiological Imaging of the Brain with PET.Academic Press,2001:402.
[103]Hurst R,Rollema H,Bertrand D.Nicotinic acetylcholine receptors:from basic science to therapeutics.Pharmacol Ther 2013,137:22-54.
[104]Lendvai B,Kassai F,Szajli A,Nemethy Z.alpha7 Nicotinic acetylcholine receptors and their role in cognition.Brain Res Bull 2013,93:86-96.
[105]Sorger D,Scheunemann M,Vercouillie J,Grossmann U,Fischer S,Hiller A,et al.Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[~(18)F]fluoro-benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydrobenzo[1,4]oxazines.Nucl Med Biol 2009,36:17-27.
[106]Giboureau N,Som IM,Boucher-Arnold A,Guilloteau D,Kassiou M.PET radioligands for the vesicular acetylcholine transporter(VAChT).Curr Top Med Chem 2010,10:1569-1583.
[107]Fujita M,Innis RB.In vivo molecular imaging:ligand development and research applications.In:Borroni E and Kupfer DJ(Eds.).Neuropsychopharmacology:The Fifth Generation of Progress.New York:Raven Press Ltd,2002,Section 3:411-425.
[108]Blower PJ.Microautoradiography.In:Mather SJ(Ed.).Current Directions in Radiopharmaceutical Research and Development.Kluwer Academic Publisher,1996:219-232.
[109]Lapchak PA,Araujo DM,Hefti F.Effects of chronic nerve growth factor treatment on hippocampal[3H]cytisine/nicotinic binding sites and presynaptic nicotinic receptor function following fimbrial transections.Neuroscience 1994,60:293-298.
[110]Rubboli F,Court JA,Sala C,Morris C,Perry E,Clementi F.Distribution of neuronal nicotinic receptor subunits in human brain.Neurochem Int 1994,25:69-71.
[111]Baddick CG,Marks MJ.An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants.Biochem Pharmacol 2011,82:828-841.
[112]Morley BJ,Kemp GE,Salvaterra P.a-Bungarotoxin binding sites in the CNS.Life Sci 1979,24:859-872.
[113]Whiteaker P,Davies AR,Marks MJ,Blagbrough IS,Potter BV,Wolstenholme AJ,et al.An autoradiographic study of the distribution of binding sites for the novelα7-selective nicotinic radioligand[~3H]-methyllycaconitine in the mouse brain.Eur J Neurosci 1999,11:2689-2696.
[114]Deuther-Conrad W,Fischer S,Hiller A,Nielsen EO,Timmermann DB,Steinbach J,et al.Molecular imaging of al nicotinic acetylcholine receptors:design and evaluation of the potent radioligand[~(18)F]NS10743.Eur J Nucl Med Mol Imaging 2009,36:791-800.
[115]Daly JW.Thirty years of discovering arthropod alkaloids in amphibian skin.J Nat Prod 1998,61:162-172.
[116]Avalos M,Parker MJ,Maddox FN,Carroll Fl,Luetje CW.Effects of pyridine ring substitutions on affinity,efficacy,and subtype selectivity of neuronal nicotinic receptor agonist epibatidine.J Pharmacol Exp Ther 2002,302:1246-1252.
[117]Deuther-Conrad W,Patt JT,Feuerbach D,Wegner F,Brust P,Steinbach J.Norchloro-fluoro-homoepibatidine:specificity to neuronal nicotinic acetylcholine receptor subtypes in vitro.Farmaco 2004,59:785-792.
[118]Deuther-Conrad W,Patt JT,Lockman PR,Allen DD,Patt M,Schildan A,et al.Norchloro-fluoro-homoepibatidine(NCFHEB)-A promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET.Eur Neuropsychopharmacol 2008,18:222-229.
[119]Smits R,Fischer S,Hiller A,Deuther-Conrad W,Wenzel B,Patt M,et al.Synthesis and biological evaluation of both enantiomers of[~(18)F]flubatine,promising radiotracers with fast kinetics for the imaging ofα_4β_2-nicotinic acetylcholine receptors.Bioorg Med Chem 2014,22:804-812.
[120]Patt JT,Spang JE,Westera G,Buck A,Schubiger PA.Synthesis and in Vivo studies of[C-11]N-methylepibatidine:comparison of the stereoisomers.Nucl Med Biol 1999,26:165-173.
[121]Molina PE,Ding YS,Carroll Fl,Liang F,Volkow ND,Pappas N,et al.Fluoro-norchloroepibatidine:preclinical assessment of acute toxicity.Nucl Med Biol 1997,24:743-747.
[122]Gandiha A,Marshall IG.The effects of 2-(4-phenylpiperidino)-cyclohexanol(AH5183)on the acetylcholine content of,and output from,the chick biventer cervicis muscle preparation.Int J Neurosci 1973,5:191-196.
[123]Prior C,Marshall IG,Parsons SM.The pharmacology of vesamicol:an inhibitor of the vesicular acetylcholine transporter.Gen Pharmacol 1992,23:1017-1022.
[124]Hicks BW,Rogers GA,Parsons SM.Purification and characterization of a nonvesicular vesamicol-binding protein from electric organ and demonstration of a related protein in mammalian brain.J Neurochem 1991,57:509-519.
[125]Kovac M,Mavel S,Deuther-Conrad W,Meheux N,Glockner J,Wenzel B,et al.3D QSAR study,synthesis,and in vitro evaluation of(+)-5-FBVM as potential PET radioligand for the vesicular acetylcholine transporter(VAChT).Bioorg Med Chem 2010,18:7659-7667.
[126]Mulholland GK,Jung YW,Wieland DM,Kilbourn MR,Kuhl DE.Synthesis of[~(18)F]fluoroethoxy-benzovesamicol,a radiotracer for cholinergic neurons.J Labelled Comp Radiopharm 1993,33:583-591.
[127]Petrou M,Frey KA,Kilbourn MR,Scott PJ,Raffel DM,Bohnen Nl,et al.In vivo imaging of human cholinergic nerve terminals with(-)-5-~(18)F-fluoroethoxybenzovesamicol:biodistribution,dosimetry,and tracer kinetic analyses.J Nucl Med 2014.doi:10.2967/jnumed.113.124792.
[128]Parent MJ,Bedard MA,Aliaga A,Minuzzi L,Mechawar N,Soucy JP,et al.Cholinergic depletion in Alzheimer's disease shown by[~(18)F]FEOBV autoradiography.Int J Mol Imaging2013,2013:205045.
[129]Szymoszek A,Wenzel B,Scheunemann M,Steinbach J,Schuurmann G.First CoMFA characterization of vesamicol analogs as ligands for the vesicular acetylcholine transporter.J Med Chem 2008,51:2128-2136.
[130]Maier CA,Wiinsch B.Novel spiropiperidines as highly potent and subtype selectiveσ-receptor ligands.Part 1.J Med Chem 2002,45:438-448.
[131]Maier CA,Wunsch B.Novel s receptor ligands.Part 2.SAR of spiro[[2]benzopyran-1,4'-piperidines]and spiro[[2]benzofuran-1,4'-piperidines]with carbon substituents in position 3.J Med Chem 2002,45:4923-4930.
[132]Maier CA,Wunsch B.Novel s receptor ligands,Part 3:Synthesis and SAR studies of 3-substituted 1'-benzylspiro[[2]benzoxepine-1,4'-piperidines].Eur J Org Chem 2003:714-720.
[133]Grolie Maestrup E,Fischer S,Wiese C,Schepmann D,Hiller A,Deuther-Conrad W,et al.Evaluation of spirocyclic3-(3-fluoropropyl)-2-benzofurans as a,receptor ligands for neuroimaging with positron emission tomography.J Med Chem 2009,52:6062-6072.
[134]Gro(?)e Maestrup E,Wiese C,Schepmann D,Brust P,W(u|¨)nsch B.Synthesis,pharmacological activity and structure affinity relationships of spirocyclic a,receptor ligands with a(2-fluoroethyl)residue in 3-position.Bioorg Med Chem 2011,19:393-405.
[135]Grolie Maestrup E,Wiese C,Schepmann D,Hiller A,Fischer S,Scheunemann M,et al.Synthesis of spirocyclic sigma(1)receptor ligands as potential PET radiotracers,structureaffinity relationships and in vitro metabolic stability.Bioorg Med Chem 2009,17:3630-3641.
[136]Holl K,Falck E,K(o|¨)hler J,Schepmann D,Humpf HU,Brust P,et al.Synthesis,characterization,and metabolism studies of fluspidine enantiomers.Chem Med Chem 2013,8:2047-2056.
[137]Maisonial A,Grosse Maestrup E,Fischer S,Hiller A,Scheunemann M,Wiese C,et al.A~(18)F-labeled fluorobutylsubstituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of a,receptors.Chem Med Chem 2011,6:1401-1410.
[138]Maisonial A,Grosse Maestrup E,Wiese C,Hiller A,Schepmann D,Fischer S,et al.Synthesis,radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for centralσ_1 receptors and comparison with fluoroalkyl homologs.Bioorg Med Chem 2012,20:257-269.
[139]Fischer S,Wiese C,Grosse Maestrup E,Hiller A,DeutherConrad W,Scheunemann M,et al.Molecular imaging of sigma receptors:synthesis and evaluation of the potentσ_1selective radioligand[~(18)F]fluspidine.Eur J Nucl Med Mol Imaging 2011,38:540-551.
[140]Bickel U.How to measure drug transport across the bloodbrain barrier.NeuroRx 2005,2:15-26.
[141]Pardridge WM.Drug transport across the blood-brain barrier.J Cereb Blood Flow Metab 2012,32:1959-1972.
[142]Kessler RM,Ansari MS,de Paulis T,Schmidt DE,Clanton JA,Smith HE,et al.High affinity dopamine D_2 receptor radioligands.1.Regional rat brain distribution of iodinated benzamides.J Nucl Med 1991,32:1593-1600.
[143]Tsuji A.Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems.NeuroRx2005,2:54-62.
[144]Ecker GF,Noe CR.In silico prediction models for blood-brain barrier permeation.Curr Med Chem 2004,11:1617-1628.
[145]Gouverneur V,Miiller K.Fluorine in Pharmaceutical and Medicinal Chemistry:From Biophysical Aspects to Clinical Applications.Singapore:World Scientific Publishing 2012.
[146]Tressaud A,Haufe G(Eds.).Fluorine and Health,Molecular Imaging,Biomedical Materials and Pharmaceuticals.Elsevier Science,2008.
[147]Alauddin MM.Positron emission tomography(PET)imaging with~(18)F-based radiotracers.Am J Nucl Med Mol Imaging2012,2:55-76.
[148]Ross TL,Wester HJ.~(18)F:Labeling chemistry and labeled compounds.In:Vertes A,Nagy S,Klencsar Z,Lovas R,Rosch F(Eds.).Handbook of Nuclear Chemistry:Radiochemistry and Radiopharmaceutical Chemistry in Life Sciences,2nd Ed.Springer,2011,4:2021-2071.
[149]Schubiger PA,Lehmann L,Friebe M.PET Chemistry:The Driving Force in Molecular Imaging.Springer,2007.
[150]Bergman J,Solin O.Fluorine-18-labeled fluorine gas for synthesis of tracer molecules.Nucl Med Biol 1997,24:677-683.
[151]Forsback S,Marjamaki P,Eskola O,Bergman J,Rokka J,Gronroos T,et al.[~(18)F]CFT synthesis and binding to monoamine transporters in rats.EJNMMI Res 2012,2:3.
[152]Ermisch A,Brust P,Kretzschmar R,Ruhle HJ.Peptides and Blood-Brain Barrier Transport.Physiol Rev 1993,73:489-527.
[153]Coenen HH,Hamacher K,Sch(u|¨)IIer M,Stocklin G,Klatte B,Kn(o|¨)chel A.Process for the preparation of fluorine-18 labelled compounds by nucleophilic exchange.EP0167103 A2,1985.
[154]Coenen HH,Colosimo M,Schuller M,Stocklin G.Preparation of n.c.a.[~(18)F]CH_2BrF via aminopolyether supported nucleophilic substitution.J Labelled Compd Radiopharm1986,23:587-595.
[155]Roeda D,Dolle F.Aliphatic nucleophilic radiofluorination.Curr Radiopharm 2010,3:81-108
[156]Cai LS,Lu SY,Pike VW.Chemistry with[~(18)F]fluoride ion.European J Org Chem 2008:2853-2873.
[157]Hoepping A,Scheunemann M,Fischer S,DeutherConrad W,Hiller A,Wegner F,et al.Radiosynthesis and biological evaluation of an~(18)F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon.Nucl Med Biol 2007,34:559-570.
[158]Deuther-Conrad W,Fischer S,Scheunemann M,Hiller A,Diekers M,Friemel A,et al.GABA_A receptor specific pyrazolopyrimidines as potential imaging agents:In vivo characteristics of a new~(18)F-labelled Indiplon derivative.Curr Radiopharm 2009,2:24-31.
[159]Fischer S,Hiller A,Scheunemann M,Deuther-Conrad W,Hoepping A,Diekers M,et al.Radiosynthesis of novel1aF-labelled derivatives of indiplon as potential GABA_A receptor imaging tracers for PET.J Labelled Comp Radiopharm 2008,51:123-131.
[160]Schirrmacher R,Bradtmoller G,Schirrmacher E,Thews O,Tillmanns J,Siessmeier T,et al.~(18)F-labeling of peptides by means of an organosilicon-based fluoride acceptor.Angew Chem Int Ed Engl 2006,45:6047-6050.
[161]R6mer J,Fuchtner F,Steinbach J,Kasch H.Automated synthesis of 16a-[~(18)F]fluoroestradiol-3,17β-disulphamate.Appl Radiat Isot 2001,55:631-639.
[162]Ermert J,Coenen HH.Nucleophilic~(18)F-fluorination of complex molecules in activated carbocyclic aromatic position.Curr Radiopharm 2010,3:109-126
[163]Fischer S,Hiller A,Smits R,Hoepping A,Funke U,Wenzel B,et al.Radiosynthesis of racemic and enantiomerically pure(-)-[~(18)F]flubatine-A promising PET radiotracer for neuroimaging ofα_4β_2 nicotinic acetylcholine receptors.Appl Radiat Isot 2013,74C:128-136.
[164]Patt JT,Deuther-Conrad W,Wohlfarth K,Feuerbach D,Brust P,Steinbach J.Norchloro-fluoro-homoepibatidine:~(18)F-labelling and evaluation of affinity and selectivity at neuronal nicotinic acetylcholine receptors.J Labelled Compd Radiopharm 2003,46(S1):S 168.
[165]Patt M,Schildan A,Habermann B,Fischer S,Hiller A,Deuther-Conrad W,et al.Fully automated radiosynthesis of both enantiomers of[~(18)F]Flubatine under GMP conditions for human application.Appl Radiat Isot 2013,80:7-11.
[166]Hockley BG,Stewart MN,Sherman P,Quesada C,Kilbourn MR,Albin RL,et al.(-)-[~(18)F]Flubatine:evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use.J Labelled Comp Radiopharm 2013,56:595-599.
[167]Ruhl T,Deuther-Conrad W,Fischer S,Gunther R,Hennig L,Krautscheid H,et al.Cannabinoid receptor type 2(CB_2)-selective N-aryl-oxadiazolyl-propionamides:synthesis,radiolabelling,molecular modelling and biological evaluation.Org Med Chem Lett 2012,2:32.
[168]Teodoro R,Moldovan RP,Lueg C,Gunther R,Donat CK,Ludwig FA,et al.Radiofluorination and biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB_2 receptors.Org Med Chem Lett 2013,3:11.
[169]Loser R,Fischer S,Hiller A,Kckerling M,Funke U,Maisonial A,et al.Use of 3-[~(18)F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines:Investigation of precursor molecules,labelling conditions and enzymatic stability of the corresponding sulfonamides.Beilstein J Org Chem 2013,9:1002-1011.
[170]Wüst F,Khler L,Berndt M,Pietzsch J.Systematic comparison of two novel,thiol-reactive prosthetic groups for~(18)F labeling of peptides and proteins with the acylation agent succinimidyl-4-[~(18)F]fluorobenzoate([~(18)F]SFB).Amino Acids2009,36:283-295.
[171]Serdons K,Verbruggen A,Bormans GM.Developing new molecular imaging probes for PET.Methods 2009,48:104-111.
[172]Pretze M,Kuchar M,Bergmann R,Steinbach J,Pietzsch J,Mamat C.An efficient bioorthogonal strategy using CuAAC click chemistry for radiofluorinations of SNEW peptides and the role of copper depletion.Chem Med Chem 2013,8:935-945.
[173]Pretze M,Pietzsch D,Mamat C.Recent trends in bioorthogonal click-radiolabeling reactions using fluorine-18.Molecules 2013,18:8618-8665.
[174]Ramenda T,Kniess T,Bergmann R,Steinbach J,Wiist F.Radiolabelling of proteins with fluorine-18 via click chemistry.Chem Commun(Camb)2009:7521-7523.
[175]Ramenda T,Steinbach J,Wust F.4-[~(18)F]Fluoro-N-methylN-(propyl-2-yn-1-yl)benzenesulfonamide([~(18)F]F-SA):a versatile building block for labeling of peptides,proteins and oligonucleotides with fluorine-18 via Cu(l)-mediated click chemistry.Amino Acids 2013,44:1167-1180.
[176]Kniess T,Laube M,Bergmann R,Sehn F,Graf F,Steinbach J,et al.Radiosynthesis of a~(18)F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2(COX-2)in vitro and in vivo.Bioorg Med Chem 2012,20:3410-3421.
[177]Funke U,Fischer S,Hiller A,Scheunemann M,DeutherConrad W,Brust P,et al.3-(4-(6-Fluoroalkoxy-3,4-dihydroisoquinoline-2(1 H)-yl)cyclohexyl)-1 H-indol e-5-carbonitriles for SERT imaging:chemical synthesis,evaluation in vitro and radiofluorination.Bioorg Med Chem Lett 2008,18:4727-4730.
[178]Funke U,Schwan G,Maisonial A,Scheunemann M,Deuther-Conrad W,Fischer S,et al.Radiosynthesis and radiotracer properties of a 7-(2-[~(18)F]fluoroethoxy)-6-methoxypyrrolidinylquinazoline for imaging of phosphodiesterase 10A with PET.Pharmaceuticals(Basel)2012,5:169-188.
[179]Sorger D,Scheunemann M,Grossmann U,Fischer S,Vercouille J,Hiller A,et al.A new~(18)F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter.Nucl Med Biol 2008,35:185-195.
[180]Hoepping A,Scheunemann M,Fischer S,DeutherConrad W,Hiller A,Wegner F,et al.Radiosynthesis and biological evaluation of an~(18)F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon.Nucl Med Biol 2007,34:559-570.
[181]Donat CK,Schuhmann MU,Voigt C,Nieber K,DeutherConrad W,Brust P.Time-dependent alterations of cholinergic markers after experimental traumatic brain injury.Brain Res2008,1246:167-177.
[182]Perry DC,Kellar KJ.[3H]epibatidine labels nicotinic receptors in rat brain:an autoradiographic study.J Pharmacol Exp Ther1995,275:1030-1034.
[183]Vaupel DB,Mukhin AG,Kimes AS,Horti AG,Koren AO,London ED.In vivo studies with[125l]5-l-A-85380,a nicotinic acetylcholine receptor radioligand.Neuroreport 1998,9:2311-2317.
[184]Davies AR,Hardick DJ,Blagbrough IS,Potter BV,Wolstenholme AJ,Wonnacott S.Characterisation of the binding of[3H]methyllycaconitine:a new radioligand for labelling a7-type neuronal nicotinic acetylcholine receptors.Neuropharmacology 1999,38:679-690.
[185]No-authors-listed.Indiplon.Indiplon modified-release,indiplon MR,NBI 34060,NBI 34060 modified-release,NBI34060 MR.Drugs R D 2002,3:197-199.
[186]Hoepping A,Diekers M,Deuther-Conrad W,Scheunemann M,Fischer S,Hiller A,et al.Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors.Bioorg Med Chem 2008,16:1184-1194.
[187]Brust P,Scheffel U,Szabo Z.Radioligands for the study of the 5-HT transporter in vivo.IDrugs 1999,2:129-145.
[188]Kretzschmar M,Brust P,Zessin J,Cumming P,Bergmann R,Johannsen B.Autoradiographic imaging of the serotonin transporter in the brain of rats and pigs using S-([~(18)F]Fluoromethyl)-(+)-McN5652.Eur Neuropsychopharmacol2003,13:387-397.
[189]Kung MP,Stevenson DA,Plssl K,Meegalla SK,Beckwith A,Essman WD,et al.[~(99m)Tc]TRODAT-1:a novel technetium-99m complex as a dopamine transporter imaging agent.European J Nucl Med 1997,24:372-380.
[190]Kung HF,Kung MP,Wey SP,Lin KJ,Yen TC.Clinical acceptance of a molecular imaging agent:a long march with[Tc-99m]TRODAT.Nucl Med Biol 2007,34:787-789.
[191]Tan PZ,Baldwin RM,Van Dyck CH,Al-Tikriti M,Roth B,Khan N,et al.Characterization of radioactive metabolites of 5-HT_(2A)receptor PET ligand[~(18)F]altanserin in human and rodent.Nucl Med Biol 1999,26:601-608.
[192]van Dyck CH,Tan PZ,Baldwin RM,Amici LA,Garg PK,Ng CK,et al.PET quantification of 5-HT_(2A)receptors in the human brain:a constant infusion paradigm with[~(18)F]altanserin.J Nucl Med 2000,41:234-241.
[193]Liptrot M,Adams KH,Martiny L,Pinborg LH,Lonsdale MN,Olsen NV,et al.Cluster analysis in kinetic modelling of the brain:a noninvasive alternative to arterial sampling.Neuroimage 2004,21:483-493.
[194]Bergstrom KA,Halldin C,Kuikka JT,Swahn CG,Tiihonen J,Hiltunen J,et al.Lipophilic metabolite of[~(123)I]β-CIT in human plasma may obstruct quantitation of the dopamine transporter.Synapse 1995,19:297-300.
[195]Lundkvist C,Halldin C,Swahn CG,Ginovart N,Farde L.Different brain radioactivity curves in a PET study with[~(11)C]B-CIT labelled in two different positions.Nucl Med Biol 1999,26:343-350.
[196]Zoghbi SS,Shetty HU,Ichise M,Fujita M,Imaizumi M,Liow JS,et al.PET imaging of the dopamine transporter with~(18)F-FECNT:a polar radiometabolite confounds brain radioligand measurements.J Nucl Med 2006,47:520-527.
[197]Shetty HU,Zoghbi SS,Liow JS,Ichise M,Hong J,Musachio JL,ef at.Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand[~(11)C]PE2I.Eur J Nucl Med Mol Imaging 2007,34:667-678.
[198]Peyronneau MA,Saba W,Dolle F,Goutal S,Coulon C,Bottlaender M,et al.Difficulties in dopamine transporter radioligand PET analysis:the example of LBT-999 using[~(18)F]and[~(11)C]labelling:part II:Metabolism studies.Nucl Med Biol2012,39:347-359.
[199]Bergstr6m KA,Halldin C,Hall H,Lundkvist C,Ginovart N,Swahn CG,et al.In vitro and in vivo characterisation of norB-CIT:a potential radioligand for visualisation of the serotonin transporter in the brain.European J Nucl Med 1997,24:596-601.
[200]Guengerich FP.Common and uncommon cytochrome P450reactions related to metabolism and chemical toxicity.Chem Res Toxicol 2001,14:611-650.
[201]Carroll Fl,Blough BE,Nie Z,Kuhar MJ,Howell LL,Navarro HA.Synthesis and monoamine transporter binding properties of 3beta-(3',4'-disubstituted phenyl)tropane-2beta-carboxylic acid methyl esters.J Med Chem 2005,48:2767-2771.
[202]Mori T,Sun LQ,Kobayashi M,Kiyono Y,Okazawa H,Furukawa T,et al.Preparation and evaluation of ethyl[~(18)F]fluoroacetate as a proradiotracer of[~(18)F]fluoroacetate for the measurement of glial metabolism by PET.Nucl Med Biol2009,36:155-162.
[203]Dienel GA,Popp D,Drew PD,Ball K,Krisht A,Cruz NF.Preferential labeling of glial and meningial brain tumors with[2-~(14)C]acetate.J Nucl Med 2001,42:1243-1250.
[204]Lear JL,Ackermann RF.Evaluation of radiolabeled acetate and fluoroacetate as potential tracers of cerebral oxidative metabolism.Metab Brain Dis 1990,5:45-56.
[205]Davson H,Segal MB.Physiology of the CSF and Blood-Brain Barriers.Boca Raton,USA:CRC Press,1996.
[206]Rogers GA,Stone-Elander S,Ingvar M,Eriksson L,Parsons SM,Widen L.~(18)F-labeiled vesamicol derivatives:syntheses and preliminary in vivo small animal positron emission tomography evaluation.Nucl Med Biol 1994,21:219-230.
[207]Tu LQ,Wright PF,Rix CJ,Ahokas JT.Is fluoroacetatespecific defluorinase a glutathione S-transferase?Comp Biochem Physiol C Toxicol Pharmacol 2006,143:59-66.
[208]Johnson JA,el Barbary A,Kornguth SE,Brugge JF,Siegel FL.Glutathione S-transferase isoenzymes in rat brain neurons and glia.J Neurosci 1993,13:2013-2023.
[209]Brust P,Hinz R,Kuwabara H,Hesse S,Zessin J,Pawelke B,et al.In vivo measurement of the serotonin transporter with(S)-([~(18)F]fluoromethyl)-(+)-McN5652.Neuropsychopharmacology 2003,28:2010-2019.
[210]Hesse S,Brust P,Mading P,Becker GA,Patt M,Seese A,et al.Imaging of the brain serotonin transporters(SERT)with~(18)F-labelled fluoromethyl-McN5652 and PET in humans.Eur J Nucl Med Mol Imaging 2012,39:1001-1011.
[211]Szabo Z,Scheffel U,Mathews WB,Ravert HT,Szabo K,Kraut M,et al.Kinetic analysis of[~(11)C]McN5652:a serotonin transporter radioligand.J Cereb Blood Flow Metab 1999,19:967-981.
[212]Brust P,Patt JT,Deuther-Conrad W,Becker G,Patt M,Schildan A,et al.In vivo measurement of nicotinic acetylcholine receptors with[~(18)F]norchloro-fluoro-homoepibatidine.Synapse 2008,62:205-218.
[213]Patt M,Becker GA,Grossmann U,Habermann B,Schildan A,Wilke S,et al.Evaluation of metabolism,plasma protein binding and other biological parameters after administration of(-)-[~(18)F]flubatine in humans.Nucl Med Biol 2014.doi.org/10.1016/j.nucmedbio.2014.1003.1018.
[214]Becker GA,Wilke S,Schonknecht P,Patt M,Luthardt J,Hesse S,et al.Comparison of(-)-[~(18)F]-flubatine and 2-[~(18)F]FA-85380 binding to nicotinic alpha4beta2 acetylcholine receptors in human brains.Eur J Nucl Med Mol Imaging2013,40(Suppl.2):S271.
[215]Fasinu P,Bouic PJ,Rosenkranz B.Liver-based in vitro technologies for drug biotransformation studies-a review.Curr Drug Metab 2012,13:215-224.
[216]Davydov DR.Microsomal monooxygenase as a multienzyme system:the role of P450-P450 interactions.Expert Opin Drug Metab Toxicol 2011,7:543-558.
[217]Stabin MG.Fundamentals of Nuclear Medicine Dosimetry.Springer,2008.
[218]van de Waterbeemd H,Camenisch G,Folkers G,Chretien JR,Raevsky OA.Estimation of blood-brain barrier crossing of drugs using molecular size and shape,and H-bonding descriptors.J Drug Target 1998,6:151-165.
[219]Ball K,Bouzom F,Scherrmann JM,Walther B,Decleves X.Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier-towards a mechanistic IVIVE-based approach.AAPS J 2013,15:913-932.
[220]Shawahna R,Decleves X,Scherrmann JM.Hurdles with using in vitro models to predict human blood-brain barrier drug permeability:a special focus on transporters and metabolizing enzymes.Curr Drug Metab 2013,14:120-136.
[221]Uchida Y,Ohtsuki S,Katsukura Y,Ikeda C,Suzuki T,Kamiie J,et al.Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors.J Neurochem2011,117:333-345.
[222]Rfitering S,Scheunemann M,Fischer S,Hiller A,Peters D,Deuther-Conrad W,et al.Radiosynthesis and first evaluation in mice of[~(18)F]NS14490 for molecular imaging of a7 nicotinic acetylcholine receptors.Bioorg Med Chem 2013,21:2635-2642.
[223]Syvanen S,Lindhe O,Palner M,Kornum BR,Rahman O,Langstr(o|¨)m B,et al.Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport.Drug Metab Dispos 2009,37:635-643.
[224]Wagner HN,Jr.,Burns HD,Dannals RF,Wong DF,Langstrom B,DuelferT,et al.Imaging dopamine receptors in the human brain by positron tomography.Science 1983,221:1264-1266.
[225]Ehrin E,Farde L,de Paulis T,Eriksson L,Greitz T,Johnstr(o|¨)m P,et al.Preparation of~(11)C-labelled Raclopride,a new potent dopamine receptor antagonist:preliminary PET studies of cerebral dopamine receptors in the monkey.Int J Appl Radiat Isot 1985,36:269-273.
[226]Chan GL,Holden JE,Stoessl AJ,Doudet DJ,Wang Y,Dobko T,et al.Reproducibility of the distribution of carbon-11-SCH23390,a dopamine D,receptor tracer,in normal subjects.J Nucl Med 1998,39:792-797.
[227]Parsey RV,Arango V,Olvet DM,Oquendo MA,Van Heertum RL,John Mann J.Regional heterogeneity of 5-HT_(1A)receptors in human cerebellum as assessed by positron emission tomography.J Cereb Blood Flow Metab 2005,25:785-793.
[228]Biver F,Goldman S,Luxen A,Monclus M,Forestini M,Mendlewicz J,et al.Multicompartmental study of F-18altanserin binding to brain 5HT_2 receptors in humans using positron emission tomography.Eur J Nucl Med 1994,21:937-946.
[229]Itoh T,Tanaka M,Kobayashi K,Suzuki K,Inoue O.Binding kinetics of~(11)C-N-methyl piperidyl benzilate(~(11)C-NMPB)in a rhesus monkey brain using the cerebellum as a reference region.Ann Nucl Med 2005,19:499-505.
[230]Deuther-Conrad W,Fischer S,Hiller A,Becker G,Cumming P,Xiong G,et al.Assessment ofα7 nicotinic acetylcholine receptor availability in porcine brain with[~(18)F]NS10743.Eur J Nucl Med Mol Imaging 2011,38:1541-1549.
[231]Flesher JE,Scheffel U,London ED,Frost JJ.In vivo labeling of nicotinic cholinergic receptors in brain with[3H]cytisine.Life Sci 1994,54:1883-1890.
[232]Ishiwata K,Kawamura K,Wang WF,Tsukada H,Harada N,Mochizuki H,et al.Evaluation of in vivo selective binding of[~(11)C]doxepin to histamine H,receptors in five animal species.Nucl Med Biol 2004,31:493-502.
[233]Kish SJ,Furukawa Y,Chang LJ,Tong J,Ginovart N,Wilson A,et al.Regional distribution of serotonin transporter protein in postmortem human brain:Is the cerebellum a SERT-free brain region?Nucl Med Biol 2005,32:123-128.
[234]Brust P,Hesse S,Müller U,Szabo Z.Neuroimaging of the serotonin transporter-possibilities and pitfalls.Curr Psychiat Rev 2006,2:111-149.
[235]Marjamaki P,Zessin J,Eskola O,Gronroos T,Haaparanta M,Bergman J,et al.S-[~(18)F]fluoromethyl-(+)-McN5652,a PET tracer for the serotonin transporter:Evaluation in rats.Synapse 2003,47:45-53.
[236]Deuther-Conrad W,Maisonial A,Patt M,Stittsworth S,Becker G,Habermann B,et al.Discovery of enantioselective suitability of(R)-(+)-and(S)-(-)-[~(18)F]fluspidine forσ_1 receptor imaging.J Label Comp Radiopharm 2013,56:S55.
[237]Brust P,Deuther-Conrad W,Becker G,Patt M,Donat CK,Stittsworth S,et al.Distinctive in vivo kinetics of the new sigmal receptor ligands(R)-(+)-and(S)-(-)-~(18)F-fluspidine in porcine brain.J Nucl Med 2014,pii:jnumed.114.137562.
[238]Leenders KL,Gibbs JM,Frackowiak RS,Lammertsma AA,Jones T.Positron emission tomography of the brain:new possibilities for the investigation of human cerebral pathophysiology.Prog Neurobiol 1984,23:1-38.
[239]Mintun MA,Raichle ME,Kilbourn MR,Wooten GF,Welch MJ.A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.Ann Neurol1984,15:217-227.
[240]Miyoshi S,Mitsuoka K,Nishimura S,Veltkamp SA.Radioisotopes in Drug Research and Development:Focus on Positron Emission Tomography.In:Singh N(Ed).Radioisotopes-Applications in Bio-Medical Science.InTech,2011:93-113.
[241]Yanai K,Ido T,Ishiwata K,Hatazawa J,Watanuki S,Takahashi T,et al.Characteristics of specific in vivo labeling of neuroleptic binding sites with 3-N-[~(11)C]methylspiperone.European J Nucl Med 1986,11:438-443.
[242]Brust P,Shaya EK,Jeffries KJ,Dannals RF,Ravert HT,Wilson AA,et al.Effects of vasopressin on blood-brain transfer of methionine in dogs.J Neurochem 1992,59:1421-1429.
[243]Kong FL,Ford RJ,Yang DJ.Managing lymphoma with nonFDG radiotracers:current clinical and preclinical applications.Biomed Res Int 2013,2013:626910.
[244]Prenen GH,Go KG,Paans AM,Zuiderveen F,Vaalburg W,Kamman RL,et al.Positron emission tomographical studies of 1-~(11)C-acetoacetate,2-~(18)F-fluoro-deoxy-D-glucose,and L-1-~(11)C-tyrosine uptake by cat brain with an experimental lesion.Acta Neurochirurgica 1989,99:166-172.
[245]Ginovart N,Wilson AA,Meyer JH,Hussey D,Houle S.[~(11)C]-DASB,a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter:PET characterization and evaluation in cats.Synapse 2003,47:123-133.
[246]Bauer R,Bergmann R,Beyer GJ,Manfrass P,Steinbach J,Kretzschmar M,et al.Investigations of cerebral glucose utilization into the newborn brain:a[~(18)F]-FDG positron emission tomography study using a high resolution multiwire proportional chamber detector device.Exp Pathol 1991,42:229-233.
[247]Sauleau P,Lapouble E,Val-Laillet D,Malbert CH.The pig model in brain imaging and neurosurgery.Animal 2009,3:1138-1151.
[248]Alstrup AKO,Smith DF.PET neuroimaging in pigs.Scand J Lab Anim Sci 2012,39:25-45.
[249]Herzog H.PET/MRI:challenges,solutions and perspectives.Z Med Phys 2012,22:281-298.
[250]Herzog H,van den Hoff J.Combined PET/MR systems:an overview and comparison of currently available options.Q J Nucl Med Mol Imaging 2012,56:247-267.
[251]Xi W,Tian M,Zhang H.Molecular imaging in neuroscience research with small-animal PET in rodents.Neurosci Res2011,doi:10.1016/j.neures.2010.12.017.
[252]Lancelot S,Zimmer L.Small-animal positron emission tomography as a tool for neuropharmacology.Trends Pharmacol Sci 2010,31:411-417.
[253]Syvanen S,Labots M,Tagawa Y,Eriksson J,Windhorst AD,Lammertsma AA,et al.Altered GABA_A receptor density and unaltered blood-brain barrier transport in a kainate model of epilepsy:an in vivo study using~(11)C-flumazenil and PET.J Nucl Med 2012,53:1974-1983.
[254]Gunn RN,Gunn SR,Turkheimer FE,Aston JA,Cunningham VJ.Positron emission tomography compartmental models:a basis pursuit strategy for kinetic modeling.J Cereb Blood Flow Metab 2002,22:1425-1439.
[255]Schmidt KC,Turkheimer FE.Kinetic modeling in positron emission tomography.Quarterly J Nucl Med 2002,46:70-85.
[256]Laruelle M,Slifstein M,Huang Y.Positron emission tomography:imaging and quantification of neurotransporter availability.Methods 2002,27:287-299.
[257]Watabe H,Ikoma Y,Kimura Y,Naganawa M,Shidahara M.PET kinetic analysis-compartmental model.Ann Nucl Med2006,20:583-588.
[258]van den Hoff J.Principles of quantitative positron emission tomography.Amino Acids 2005,29:341-353.
[259]van den Hoff J.Kinetic Modelling.In:Kiessling F,Pichler BJ.Small Animal Imaging:Basics and Practical Guide.Springer,2010:387-404.
[260]Brust P,Zessin J,Kuwabara H,Pawelke B,Kretzschmar M,Hinz R,et al.Positron emission tomography imaging of the serotonin transporter in the pig brain using[~(11)C](+)-McN5652and S-([~(18)F]fluoromethyl)-(+)-McN5652.Synapse 2003,47:143-151.
[261]Lammertsma AA,Bench CJ,Hume SP,Osman S,Gunn K,Brooks DJ,et al.Comparison of methods for analysis of clinical C-11 raclopride studies.J Cereb Blood Flow Metab1996,16:42-52.
[262]Lammertsma AA,Hume SP.Simplified reference tissue model for PET receptor studies.Neuroimage 1996,4:153-158.
[263]Wang G,Qi J.Direct estimation of kinetic parametric images for dynamic PET.Theranostics 2013,3:802-815.
[264]Patlak CS,Blasberg RG,Fenstermacher JD.Graphical evaluation of blood-to-brain transfer constants from multipletime uptake data.J Cereb Blood Flow Metab 1983,3:1-7.
[265]Patlak CS,Blasberg RG.Graphical evaluation of bloodto-brain transfer constants from multiple-time uptake data.Generalizations.J Cereb Blood Flow Metab 1985,5:584-590.
[266]Gjedde A.High-and low-affinity transport of D-glucose from blood to brain.J Neurochem 1981,36:1463-1471.
[267]Logan J,Fowler JS,Volkow ND,Wolf AP,Dewey SL,Schlyer DJ,et al.Graphical analysis of reversible radioligand binding from time-activity measurements applied to[N-~(11)C-methyl]-(-)-cocaine PET studies in human subjects.J Cereb Blood Flow Metab 1990,10:740-747.
[268]Wang JZ,Qiu P,Liu RKJ,Szabo Z.Model-Based receptor quantization analysis for PET parametric imaging.Conf Proc IEEE Eng Med Biol Soc 2005,6:5908-5911.
[269]Dennan S,Decristoforo Ce.The Radiopharmacy.A Technologist's Guide.European Association of Nuclear Medicine,2008.
[270]Elsinga P,Todde S,Penuelas I,Meyer G,Farstad B,FaivreChauvet A,et al.Guidance on current good radiopharmacy practice(cGRPP)for the small-scale preparation of radiopharmaceuticals.Eur J Nucl Med Mol Imaging 2010,37:1049-1062.
[271]Verbruggen A,Coenen HH,Deverre JR,Guilloteau D,Langstrom B,Salvadori PA,et al.Guideline to regulations for radiopharmaceuticals in early phase clinical trials in the EU.Eur J Nucl Med Mol Imaging 2008,35:2144-2151.
[272]Zessin J,Eskola O,Steinbach J,Bergman J,Marjamaki P,Brust P,et al.Synthesis and first biological evaluation of the[~(18)F]fluormethyl-analog of(+)-MCN5652,a tracer for imaging the serotonin transporter.Nuklearmedizin 2000,39:A36.[Article in German language]
[273]Petrou M,Koeppe R,Scott P,Bohnen N,Kilbourn M,Frey K.PET imaging of the vesicular acetylcholine transporter.J Nucl Med 2012,53(Supplement 1):290.
[274]Farde L,Ehrin E,Eriksson L,Greitz T,Hall H,Hedstrom CG,et a/.Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.Proc Natl Acad Sci U S A 1985,82:3863-3867.
[275]Maziere M,Hantraye P,Prenant C,Sastre J,Comar D.Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[~(11)C]methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate(RO15.1788-~(11)C):a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.Int J Appl Radiat Isot 1984,35:973-976.
[276]Rowland DJ,Cherry SR.Small-animal preclinical nuclear medicine instrumentation and methodology.Semin Nucl Med2008,38:209-222.