Evaluation of [F]F-PTTP as a Positron Emission Tomography Radioligand for Imaging P2X7 Receptors in Epileptic Rats.

Patients with epilepsy often face significant challenges, with one-third of them being resistant to available antiseizure medications, leading to drug-resistant epilepsy (DRE). The P2X7 receptor (P2X7R), a mechanistic and inflammatory biomarker, exhibits increased expression during epileptogenesis. P2X7R antagonists effectively reduce the severity of seizure and neuronal death, highlighting this receptor as a potential therapeutic target. Precise detection of P2X7R is essential for guiding the treatments. Herein, we prepared the P2X7R-targeting probe [F]F-PTTP and evaluated its efficacy in positron emission tomography (PET) imaging of epileptic rats. [F]F-PTTP was synthesized via the cleavage of the trifluoromethylsulfonyl group with a radiochemical yield of 10-17% (end of synthesis, EOS), molar activity of 56.12 ± 6.06 GBq/μmol (EOS), and radiochemical purity exceeding 99%. [F]F-PTTP PET imaging was performed on epileptic rats induced via intrahippocampal kainic acid (KA) injection across three disease progression stages: acute (1 day), latent (1 week), and chronic (1 month). PET results revealed specific [F]F-PTTP binding to the epileptic brain, particularly in the right hippocampus (KA-injected site), with the highest standardized uptake value ratio observed at 1 week (1.34 ± 0.11). Autoradiography and histological analyses confirmed P2X7R overexpression in the epileptic brain, associated with microglia and astrocyte activation. Our findings suggest that [F]F-PTTP PET imaging is a promising tool for visualizing P2X7R expression during epileptogenesis, which may facilitate neuroinflammation assessment, P2X7R-targeted therapy, and treatment monitoring in epilepsy.