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内容記述 |
Background: The stroke induces neuronal damages via hypoxia, resulting in neuroimmflamation accompanied with microglial activation. The translocator protein 18kDa (TSPO) is a hallmark for microglial activation. Previously, we have developed [18F]FEDAC as a useful TSPO radioligand, which was recently used in clinical study. Herein, we conducted quantitative PET analysis of [18F]FEDAC using transient middle cerebellar artery occlusion (tMCAO) model rat for the first time. Methods: Prior to PET assessment, rats acquired tMCAO surgery with an intraluminal occlusion of one-hour under anesthesia. After 7–8 days, the rat, in which catheter was inserted into the femoral artery for blood sampling, was placed on the custom-designed chamber of a small-animal PET scanner (Inveon). Dynamic PET scans with blood sampling were conducted for 60 min after the [18F]FEDAC injection (20 MBq/head). Kinetic analyses were performed by two-tissue compartment model (2TCM), Logan graphical analysis (Logan GA) and simplified reference tissue model.Results: The respective distribution volume (VT), a macro parameter consisted in the K1–k4 rate constants in 2TCM, in the ipsilateral and contralateral areas of tMCAO rat brain was 5.4 and 2.0 mL/cm3, which corresponded to that in Logan GA. The influx rate (K1) of [18F]FEDAC in ipsilateral area of tMCAO rat brain was 0.38 mL/cm3/min, which was roughly two-times higher than contralateral area. These results suggested that high VT value in ipsilateral area of tMCAO rat brain included not only upregulation of TSPO expressions but also dysfunction of blood-brain barrier (BBB). Interestingly, the binding potential (BPND) of [18F]FEDAC with TSPO in the ipsilateral area of tMCAO rat brain was improved by cerebral blood flow (CBF) correction, in which heterogeneous signal for corrected BPND in PET image was consistent with immunohistochemical intensity for TSPO expressions.Conclusion: We successfully visualized only TSPO expressions excluding the dysfunction of BBB in PET images scaled with CBF-corrected BPND. |
