Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan.
J Cereb Blood Flow Metab. 2014 Apr;34(4):708-14. doi: 10.1038/jcbfm.2014.5. Epub 2014 Jan 22.
To assess the capability of (18)F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ((18)F-BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a specific marker of ischemia-induced neuronal death without being disturbed by inflammation, translational research was conducted using an animal PET in ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hours, then PET scans were conducted at Day-7 with (15)O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolism of oxygen (rCMRO₂), and (18)F-BCPP-EF for MC-I with arterial blood sampling. On Day-8, the additional PET scans conducted with (11)C-flumazenil ((11)C-FMZ) for central-type benzodiazepine receptors, (11)C-PBR28 for translocator protein, and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) for regional cerebral metabolic rate of glucose (rCMRglc). The total distribution volume (VT) values of (18)F-BCPP-EF showed the significant reduction in MC-I activity in the damaged area at Day-7. When correlated with rCBF and rCMRO₂, the VT values of (18)F-BCPP-EF provided better correlation with rCMRO₂ than with rCBF. In the inflammatory regions (region of interest, ROIPBR) of the ischemic hemisphere detected with (11)C-PBR28, higher (18)F-FDG uptake and lower VT of (18)F-BCPP-EF, (11)C-FMZ, and rCMRO2 than those in normal contralateral hemisphere were observed. These results strongly suggested that (18)F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where (18)F-FDG could not owing to its high uptake into the activated microglia.
为评估新型正电子发射断层扫描（PET）探针（18）F-2-叔丁基-4-氯-5-[6-[2-（2-乙氧基）乙氧基]-3-吡啶甲氧基]-2H-哒嗪-3-酮（（18）F-BCPP-EF）检测线粒体复合物 I（MC-I）活性的能力，我们在恒河猴（Macaca fascicularis）缺血性脑动物 PET 中进行了转化研究。通过右侧大脑中动脉闭塞 3 小时诱导局灶性缺血，然后在第 7 天用（15）O-气体进行 PET 扫描以评估局部脑血流（rCBF）和局部脑氧代谢（rCMRO₂），并使用动脉血取样进行（18）F-BCPP-EF 检测 MC-I。在第 8 天，用（11）C-flumazenil（（11）C-FMZ）进行中央型苯二氮䓬受体、（11）C-PBR28 进行转位蛋白和（18）F-氟-2-脱氧-D-葡萄糖（（18）F-FDG）进行局部脑葡萄糖代谢率（rCMRglc）的 PET 扫描。在第 7 天，（18）F-BCPP-EF 的总分布容积（VT）值显示 MC-I 活性在损伤区域显著降低。与 rCBF 和 rCMRO₂ 相关时，（18）F-BCPP-EF 的 VT 值与 rCMRO₂ 的相关性优于 rCBF。在（11）C-PBR28 检测到的缺血半球的炎症区域（ROI-PBR）中，与正常对侧半球相比，（18）F-FDG 摄取更高，（18）F-BCPP-EF、（11）C-FMZ 和 rCMRO₂的 VT 值更低。这些结果强烈表明，（18）F-BCPP-EF 可以区分伴有神经炎症的神经损伤区域，而（18）F-FDG 由于其被激活的小胶质细胞摄取而无法区分。
