Synthesis and evaluation of a novel 99mTcN(PNP)-complex with metronidazole isocyanide ligand as a marker for tumor hypoxia

详细信息    查看全文

• 作者：Kusum Vats ; Madhava B. Mallia ; Anupam Mathur…
• 关键词：Hypoxia ; Metronidazole ; Isocyanide ; [99mTcN]2+ core ; [99mTcN(PNP)]2+ core ; Biodistribution
• 刊名：Journal of Radioanalytical and Nuclear Chemistry
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：308
• 期：1
• 页码：363-369
• 全文大小：585 KB
• 参考文献：1.Wiebe LI, Machulla HJ (1999) In: Machulla HJ (ed) Imaging hypoxia. Kluwer Academic Publishers, Netherlands
  2.Ballinger JR (2001) Imaging hypoxia in tumors. Semin Nucl Med 31:321–329CrossRef
  3.Mees G, Dierckx R, Vangestel C, Van de Wiele C (2009) Molecular imaging of hypoxia with radiolabelled agents. Eur J Nucl Med Mol Imaging 36:1674–1686CrossRef
  4.Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943
  5.Krohn KA, Link JM, Mason RP (2008) Molecular imaging of hypoxia. J Nucl Med 49(Suppl 2):129S–148SCrossRef
  6.Grunbaum Z, Freauff SJ, Krohn KA, Wilbur DS, Magee S, Rasey JS (1987) Synthesis and characterization of congeners of misonidazole for imaging hypoxia. J Nucl Med 28:68–75
  7.Sorger D, Patt M, Kumar P, Wiebe LI, Barthel H, Seese A, Dannenberg C, Tannapfel A, Kluge R, Sabri O (2003) [18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nucl Med Biol 30:317–326CrossRef
  8.Foo SS, Abott DF, Lawrentschuk N, Scott AM (2004) Functional imaging of intratumoural hypoxia. J Mol Imaging Biol 6:291–305CrossRef
  9.Lee ST, Scott AM (2007) Hypoxia positron emission tomography imaging with 18F-fluoro misonidazole. Semin Nucl Med 37:451–461CrossRef
  10.Komar G, Seppänen M, Eskola O, Lindholm P, Grönroos TJ, Forsback S, Sipilä H, Evans SM, Solin O, Minn H (2008) 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med 49:1944–1951CrossRef
  11.Rajendran JG, Krohn KA (2015) F-18 fluoromisonidazole for imaging tumor hypoxia: imaging the microenvironment for personalized cancer therapy. Semin Nucl Med 45:151–162CrossRef
  12.Bonnitcha PD, Bayly SR, Theobald MB, Betts HM, Lewis JS, Dilworth JR (2010) Nitroimidazole conjugates of bis(thiosemicarbazonato)64Cu(II)—potential combination agents for the PET imaging of hypoxia. J Inorg Biochem 104:126–135CrossRef
  13.Zha Z, Zhu L, Liu Y, Du F, Gan H, Qiao J, Kung HF (2011) Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging. Nucl Med Biol 38:501–508CrossRef
  14.Mallia MB, Subramanian S, Mathur A, Sarma HD, Venkatesh M, Banerjee S (2010) Synthesis and evaluation of 2-, 4-,5-substituted nitroimidazole-iminodiacetic acid-99mTc(CO)3 complexes to target hypoxic tumors. J Label Compd Radiopharm 53:535–542CrossRef
  15.Mallia MB, Kumar C, Mathur A, Sarma HD, Banerjee S (2012) On the structural modification of 2-nitroimidazole-99mTc(CO)3 complex, a hypoxia marker, for improving in vivo pharmacokinetics. Nucl Med Biol 39:1236–1242CrossRef
  16.Mallia MB, Subramanian S, Mathur A, Sarma HD, Venkatesh M, Banerjee S (2008) On the isolation and evaluation of a novel unsubstituted 5-nitroimidazole derivative as an agent to target tumor hypoxia. Bioorg Med Chem Lett 18:5233–5237CrossRef
  17.Mallia MB, Subramanian S, Banerjee S, Sarma HD, Venkatesh M (2006) Evaluation of 99mTc(CO)3 complex of 2-methyl-5-nitroimidazole as an agent for targeting tumor hypoxia. Bioorg Med Chem 14:7666–7670CrossRef
  18.Mallia MB, Subramanian S, Mathur A, Sarma HD, Banerjee S (2014) A study on nitroimidazole-99mTc(CO)3 complexes as hypoxia marker: some observations towards possible improvement in vivo efficacy. Nucl Med Biol 41:600–610CrossRef
  19.Giglio J, Fernandez S, Pietzsch HJ, Dematteis S, Moreno M, Pacheco JP, Cerecetto H, Rey A (2012) Synthesis, in vitro and in vivo characterization of novel 99mTc-’4+1’-labeled 5-nitroimidazole derivatives as potential agents for imaging hypoxia. Nucl Med Biol 39:679–686CrossRef
  20.Fernandez S, Dematteis S, Giglio J, Cerecetto H, Rey A (2013) Synthesis, in vitro and in vivo characterization of two novel 68Ga-labelled 5-nitroimidazole derivatives as potential agents for imaging hypoxia. Nucl Med Biol 40:273–279CrossRef
  21.Liu S, Edwards DS (1999) 99mTc-labeled small peptides as diagnostic radiopharmaceuticals. Chem Rev 99:2235–2268CrossRef
  22.Banerjee S, Pillai MRA, Ramamoorthy N (2001) Evolution of Tc-99m in diagnostic radiopharmaceuticals. Semin Nucl Med 4:260–277CrossRef
  23.Banerjee SR, Maresca KP, Francesconi L, Valliant J, Babich JW, Zubieta J (2005) New directions in the coordination chemistry of 99mTc: a reflection on technetium core structures and a strategy for new chelate design. Nucl Med Biol 32:1–20CrossRef
  24.Baldas J, Bonnyman J (1985) Substitution reactions of 99mTcNCl4 −—a route to a new class of 99mTc-radiopharmaceuticals. Int J Appl Radiat Isot 36:133–139CrossRef
  25.Alberto R, Schibli R, Egli A, Schubiger PA, Abram U, Kaden TA (1998) A novel organometallic aqua complex of technetium for the labeling of biomolecules: synthesis of [99mTc(H2O)3(CO)3]+ from [99mTcO4]− in aqueous solution and its reaction with a bifunctional ligand. J Am Chem Soc 120:7987–7989CrossRef
  26.Pasqualini R, Comazzi V, Bellande E, Duatti A, Marchi A (1992) A new efficient method for the preparation of 99mTc-radiopharmaceuticals containing the TcN multiple bond. Appl Radiat Isot 43:1329–1333CrossRef
  27.Marchi A, Rossi R, Marvelli L (1993) Nitrido-technetium (V) complexes with amino acids: preparation and X-ray crystal structure of the l -cysteinate ethyl ester technetium (V) complex. Inorg Chem 32:4673–4674CrossRef
  28.Pasqualini R, Duatti A, Bellande E, Comazzi V, Brucato V, Hoffschir D, Fagret D, Comet M (1994) Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents. J Nucl Med 35:334–341
  29.Bolzati C, Boschi A, Uccelli L, Tisato F, Refesco F, Cagnolini A, Duatti A, Prakash S, Bandoli G, Vittadini A (2002) Chemistry of the strong electrophilic metal fragment [99Tc(N)(PXP)]2+ (PXP = diphosphine ligand). A novel tool for the selective labeling of small molecules. J Am Chem Soc 124:11468–11479CrossRef
  30.Bolzati C, Mahmood A, Malago E, Uccelli L, Boschi A, Jones AG, Refesco F, Duatti A, Tisato F (2003) The [99mTc(N)(PNP)]2+ metal fragment: a technetium-nitrido synthon for use with biologically active molecules. The N-(2-methoxy phenyl) piperazyl-cysteine analogues as examples. Bioconjug Chem 14:1231–1242CrossRef
  31.Bolzati C, Benini E, Cazzola E, Jung C, Tisato F, Refesco F, Pietzsch HJ, Spies H, Uccelli L, Duatti A (2004) Synthesis, characterization and biological evaluation of neutral nitride technetium (V) mixed ligand complexes containing dithiolates and aminodiphosphines. A novel system for linking technetium to biomolecules. Bioconjug Chem. 15:628–637CrossRef
  32.Mathur A, Mallia MB, Banerjee S, Sarma HD, Pillai MRA (2013) Preparation and evaluation of a 99mTcN-PNP complex of sanazole analogue for detecting tumor hypoxia. Bioorg Med Chem Lett 23:1394–1397CrossRef
  33.Bolzati C, Cavazza-Ceccato M, Agostini S, Tokunaga S, Casara D, Bandoli G (2008) Subcellular distribution and metabolism studies of the potential myocardial imaging agent [99mTc(N)(DBODC)(PNP5)]+. J Nucl Med 49:1336–1344CrossRef
  34.Taillefer R, Laflamme L, Dupras G, Picard M, Phaneuf DC, Leveille J (1988) Myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile (MIBI): comparison of short and long time intervals between rest and stress injections. Eur J Nucl Med 13:515–522CrossRef
  35.Baker RJ, Bellen JC, Fornasiero D, Penglis S (1986) The preparation of 99mTc-tertiarybutylisonitrile (99mTc-TBI) by a method suitable for routine clinical use. Int J Radiat Appl Instrum B 13:527–532CrossRef
  36.Kothari KK, Satpati D, Joshi S, Venkatesh M, Ramamoorthy N, Pillai MR (2005) 99mTc carbonyl t-butyl isonitrile: a potential new agent for myocardial perfusion imaging. Nucl Med Comm. 26:155–161CrossRef
  37.Zhang XZ, Wang XB, Jia F, Tang ZG, Zhang JB, Liu BL (2002) Preparation, characterization and biodistribution of a new technetium-99m nitrido complex with 2-methoxyisobutylisomtrile and comparison with Tc-99m-MIBI. J Label Compd Radiopharm 45:1029–1043CrossRef
  38.Zhang XZ, Wang XB, Zhou JM (2001) Preparation, characterization and biodistribution of a new technetium-99m nitrido complex with cyclohexylisonitrile. J Label Compd Radiopharm. 44:S651–S653CrossRef
  39.Zhang XZ, Wang XB, Zhou JM (2003) A new technetium-99m labeled isonitrile complex 99mTc-TMCHI as a potential blood pool imaging agent. Appl Radiat Isot 59:231–235CrossRef
  40.Dhake KP, Tambade PJ, Singhal RS, Bhanage BM (2011) An efficient, catalyst and solvent free N-formylation of aromatic and aliphatic amines. Green Chem Lett Rev 4:151–157CrossRef
  41.Kobayashi G, Saito T, Kitano Y (2011) A novel method for preparing isocyanides from N-substituted formamides with chlorophosphate compounds. Synthesis 20:3225–3234
  42.Mallia MB, Mathur A, Subramanian S, Banerjee S, Sarma HD, Venkatesh M (2005) A novel [99mTcN]2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia. Bioorg Med Chem Lett 15:3398–3401CrossRef
  43.Giglio J, Fernandez S, Rey A, Cerecetto H (2011) Synthesis and biological characterization of novel dithiocarbamate containing 5-nitroimidazole 99mTc-complexes as potential agents for targeting hypoxia. Bioorg Med Chem Lett 21:394–397CrossRef
  
• 作者单位：Kusum Vats (1)
  Madhava B. Mallia (1)
  Anupam Mathur (3)
  Haldhar D. Sarma (2)
  Sharmila Banerjee (1)
  
  1. Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
  3. Medical and Biological Products Program, Board of Radiation and Isotope Technology, Mumbai, 400705, India
  2. Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Nuclear Chemistry
  Physical Chemistry
  Nuclear Physics, Heavy Ions and Hadrons
  Diagnostic Radiology
  Inorganic Chemistry
  
• 出版者：Akad茅miai Kiad贸, co-published with Springer Science+Business Media B.V., Formerly Kluwer Academic
• ISSN：1588-2780

文摘

The [99mTcN(PNP)]2+ core offers a unique route for the preparation of asymmetric 99mTc-complexes. Though bidentate chelators such as dithiocarbamates are most commonly used ligands in this approach, present study explores the possibility of using a monodentate ligand, a isocyanide derivative of metronidazole (MetroNC), for preparing a 99mTcN(PNP) complex for detecting tumor hypoxia. MetroNC could be prepared in good yield and subsequently radiolabeled with [99mTcN(PNP)]2+ precursor complex prepared from [99mTcN]2+ core and N-(2-methoxyethyl)-2-(diphenylphosphino)-N-(2-(diphenylphosphino)ethyl)ethanamine (PNP2) ligand. Preliminary biodistribution studies showed tumor uptake pattern similar to previous studies wherein, about 75 % of the tumor activity observed at 60 min post injection (p.i.) was still found to remain in tumor at 180 min p.i.