Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET
Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET
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DOI：
10.1007/s00259-013-2628-z
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发表时间：
2014-04-01
影响因子：
9.1
通讯作者：
Harada, Norihiro
中科院分区：
文献类型：
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作者：
Tsukada, Hideo;Ohba, Hiroyuki;Harada, Norihiro
目的研究一种新的PET探针F-18-2-叔丁基-4-氯-5-{6-[2-（2-氟乙氧基）乙氧基]-吡啶-3-基甲氧基}-2H-哒嗪-3-酮（F-18-BCPP-EF），用于活体大鼠脑线粒体复合物1（MC-1）活性的定量显像。为临床应用在人类，在猴子translational research carried out.Methods PET测量与F-18-BCPP-EF进行了年轻和年老的猴子（猕猴）在清醒状态下与动脉血采样。用MC-1特异性抑制剂鱼藤酮评价F-18-BCPP-EF的结合特异性。的结合结果F-BCPP-EF在静脉注射后即刻即被脑内摄取，在注射后10 ~ 20 min达到高峰，在注射后10 ~ 20 min达到高峰。然后逐渐被淘汰。2-TC分析提供了比1-TC分析更好的拟合，2-TC分析的V（T）值与Logan图的V（T）值相关性良好。与鱼藤酮预给药相比，F-18-BCPP-EF在脑中显示出更高的摄取峰，随后比在溶剂条件下更快地消除，导致所有区域的2-TC V-T值显著降低。在老年动物中，F-18-BCPP-EF的动力学稍慢，峰值水平较低，比年轻的动物，导致年龄相关的减少F-18-BCPP-EF结合在所有的脑regions.Conclusion本研究表明，F-18-BCPP-EF可能是一个潜在的PET探针定量成像MC-1活性在活脑使用PET。
Purpose We have reported on the development of a novel PET probe, F-18-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (F-18-BCPP-EF), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in the brain of the living rat. For clinical application in humans, translational research in the monkey was conducted.Methods PET measurements with F-18-BCPP-EF were performed in young and old monkeys (Macaca mulatta) in a conscious state with arterial blood sampling. The binding specificity of F-18-BCPP-EF was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. The binding (total distribution volume, V (T)) of F-18-BCPP-EF was calculated using Logan graphical analysis, and one-tissue compartment model (1-TC) and two-tissue compartment model (2-TC) analyses using a metabolite-corrected plasma input function.Results F-BCPP-EF was rapidly taken up into the brain just after intravenous injection, peaked between 10 and 20 min after injection, and was then gradually eliminated. The 2-TC analysis provided a better fit than the 1-TC analysis, and the V (T) values from the 2-TC analysis correlated well with those from the Logan plot. With predosing with rotenone, F-18-BCPP-EF showed a higher uptake peak in the brain, followed by more rapid elimination thereafter than in the vehicle condition, resulting in significant reductions in 2-TC V-T values in all regions. In old animals, the kinetics of F-18-BCPP-EF were slightly slower with lower peak levels than in young animals, resulting age-related reductions in F-18-BCPP-EF binding in all brain regions.Conclusion The present study demonstrated that F-18-BCPP-EF may be a potential PET probe for quantitative imaging MC-1 activity in the living brain using PET.