Longitudinal Positron Emission Tomography Imaging with P2X7 Receptor-Specific Radioligand 18 F-FTTM in a Kainic Acid Rat Model of Temporal Lobe Epilepsy.

P2X7 receptors (P2X7R), as a brain inflammation biomarker, play important roles in the epileptogenic progress. Mounting evidence supports their activation in the brain during epilepsy, and inhibition of the P2X7 receptor reduces the seizure frequency and severity. In this study, we investigate P2X7R-targeted (F-FTTM) position emission tomography (PET) imaging in a rat model of temporal lobe epilepsy to obtain further insights into the role of P2X7R during epileptogenesis. F-FTTM (5-10% radiochemical yield, over 99% radiochemical purity, and a specific activity of 270-300 MBq/nmol, = 6, EOS) was first synthesized. Then, the rat models induced by intrahippocampal injection of saline (1.2 μL, = 15) or kainic acid (1.2 μL, 0.5 μg/μL, = 35) were examined using F-FTTM Micro-PET/CT longitudinal imaging, respectively. The imaging results showed that increases in the F-FTTM uptake was evident after status epilepticus (SE) in the epileptogenesis-associated brain regions, such as the hippocampus, amygdala, or temporal cortex, and this peaked during the latent period. The histopathological analysis revealed that the P2X7R PET uptake reached a peak at 7 days after SE and was mostly related to microglial activation. Thus, P2X7R-targeted PET imaging agent F-FTTM may act as a useful tool for identifying brain inflammation during epilepsy. P2X7R PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor treatment response, and it warrants further clinical studies.