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 (18F-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. 18F-FTTM (5–10% radiochemical yield,
over 99% radiochemical purity, and a specific activity of 270–300
MBq/nmol, n = 6, EOS) was first synthesized. Then,
the rat models induced by intrahippocampal injection of saline (1.2
μL, n = 15) or kainic acid (1.2 μL, 0.5
μg/μL, n = 35) were examined using 18F-FTTM Micro-PET/CT longitudinal imaging, respectively. The
imaging results showed that increases in the 18F-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 18F-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.