PET/CT脑成像新药研究发展趋势及基于PET/CT设备的脑成像新药研发
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摘要
脑部分子影像对于脑功能和神经疾病发病机理研究以及早期诊断有重大意义,多巴胺受体系统与人的情绪、爱情、成瘾、奖励机制和一些疾病有重要的联系。本文以新型脑神经多巴胺受体D2/D3显像剂~(18)F-fallypride为例,探讨了~(18)F-fallypride的研究发展和应用趋势,并应用自主研发的AMICRay-Scan 64 PET/CT成像系统对15例健康志愿者进行了临床研究,图像上观测到纹状体和外纹状体的信号清晰,药物分布均匀、对称。此外,脑肿瘤细胞凋亡显像剂~(18)F-ML-10新药可对脑肿瘤的放射性治疗效果进行评估,本文综述了~(18)F-ML-10临床应用的发展,并对10例脑瘤患者接受放射性治疗前后的细胞凋亡情况进行了对比评估,并通过图像对放射性治疗给出评价。
Brain molecular imaging plays an important role in investigations on the function of brain and mechanism of neural diseases.The dopaminergic receptor system is closely related with emotion,love,addiction,incentives,many diseases and disorders.Hereby,taking ~(18)F-fallypride as an example of novel dopamine receptor D2/D3 probes visualizing the Dopamine D2/D3 receptors in striatal and extra-striatal areas,this paper reviews the trends of R&D(Research and Development) and clinical applications of ~(18)F-fallypride,and investigates ~(18)F-fallypride with 15 healthy volunteers' brain imaging by using the self-innovated AMIC Ray-Scan 64 PET/CT.The result shows a homogeneous and symmetrical distribution of signal in striatal and extra-striatal areas,indicating that the ~(18)F-fallypride,as well as Ray-Scan 64 PET/CT,has demonstrated an excellent performance in dopamine receptor imaging.Additionally,this paper also reviews the progress of clinical uses of ~(18)F-ML-10,a molecular probe to visualize apoptosis.Besides,10 patients with brain tumorsare investigated by ~(18)F-ML-10-PET/CT imaging pre- and post- radiation with AMIC Ray-Scan 64 PET/CT,in order to evaluate the effect of treatments.
Brain molecular imaging plays an important role in investigations on the function of brain and mechanism of neural diseases.The dopaminergic receptor system is closely related with emotion,love,addiction,incentives,many diseases and disorders.Hereby,taking ~(18)F-fallypride as an example of novel dopamine receptor D2/D3 probes visualizing the Dopamine D2/D3 receptors in striatal and extra-striatal areas,this paper reviews the trends of R&D(Research and Development) and clinical applications of ~(18)F-fallypride,and investigates ~(18)F-fallypride with 15 healthy volunteers' brain imaging by using the self-innovated AMIC Ray-Scan 64 PET/CT.The result shows a homogeneous and symmetrical distribution of signal in striatal and extra-striatal areas,indicating that the ~(18)F-fallypride,as well as Ray-Scan 64 PET/CT,has demonstrated an excellent performance in dopamine receptor imaging.Additionally,this paper also reviews the progress of clinical uses of ~(18)F-ML-10,a molecular probe to visualize apoptosis.Besides,10 patients with brain tumorsare investigated by ~(18)F-ML-10-PET/CT imaging pre- and post- radiation with AMIC Ray-Scan 64 PET/CT,in order to evaluate the effect of treatments.
引文
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[14]M J Oborski,C M Laymon,Y Qian,et al.Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10[J].Translational Oncology,2014,7:111-119.
[15]Y Lu,K Yang,K Zhou,B Pang,et al.An Integrated QuadModality Molecular Imaging System for Small Animals[J].Journal of Nuclear Medicine,2014,8.
[2]R Weissleder,M J Pittet.Imaging in the era of molecular oncology[J].Nature,2008,452:580-589.
[3]J H(o|¨)glund.A Shirvan,G Antom,et al.~(18)F-ML-10,a PET Tracer for Apoptosis:First Human Study[J].Journal of Nuclear Medicine,2011,52(5):720-725.
[4]A Allen,M Ben-Ami,A Reshef,et al.Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with~(18)F-ML-10[J].European Journal of Nuclear Medicine and Molecular Imaging,2012,39:1400-1408.
[5]N Tolboom,H W Berendse,J E Leysen,et al.The Dopamine Stabilizer(-)-OSU6162 Occupies a Subpopulation of Striatal Dopamine D2/D3 Receptors:An[lsqb]HC[rsqb]Raclopride PET Study in Healthy Human Subjects[J].Neuropsychopharmac ology,2015,40:472-479.
[6]M Slifstein,L S Kegeles,X Xu,et al.Striatal and extrastriatal dopamine release measured with PET and[~(18)F]fallypride[J].Synapse,2010,64:350-362.
[7]A Egerton,M A Mehta,A J Montgomery,et al.The dopaminergic basis of human behaviors:A review of molecular imaging studies[J].Neuroscience&Biobehavioral Reviews,2009,33:1109-1132.
[8]J Ceccarini,E Vrieze,M Koole,et al.Optimized In Vivo Detection of Dopamine Release Using~(18)F-Fallypride PET[J].Journal of Nuclear Medicine,2012,53(10):1565-1572.
[9]A Nagano-Saito,A Dagher,L Booij,et al.Stress-induced dopamine release in human medial prefrontal cortex-~(18)F-Fallypride/PET study in healthy volunteers[J].Synapse,2013,67:821-830.
[10]J Guo,W K Simmons,P Herscovitch,et al.Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior[J].Mol Psychiatry,2014,19:1078-1084.
[11]N L Jansen,R Feuerecker,S Becker-Bense,et al.Assessment of cerebral dopamine D_{2/3}-receptors in patients with bilateral vestibular failure[J].Journal of Vestibular Research,2014,24:403-413.
[12]E C A Kaal,C G J H Ni(e|¨)l,C J Vecht.Therapeutic management of brain metastasis[J].The Lancet Neurology,2005,4:289-298.
[13]R Aloya,A Shirvan,H Grimberg,et al.Molecular imaging of cell death in vivo by a novel small molecule probe[J].Apoptosis,2006,11:2089-2101.
[14]M J Oborski,C M Laymon,Y Qian,et al.Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10[J].Translational Oncology,2014,7:111-119.
[15]Y Lu,K Yang,K Zhou,B Pang,et al.An Integrated QuadModality Molecular Imaging System for Small Animals[J].Journal of Nuclear Medicine,2014,8.