Synthesis and evaluation of TSPO-targeting radioligand ¹⁸FF-TFQC for PET neuroimaging in epileptic rats

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand ¹⁸FF-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, ¹⁸FF-TFQC was synthesized with a radiochemical yield of 8%–10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that ¹⁸FF-TFQC exhibited good biochemical properties, ¹⁸FF-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific ¹⁸FF-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, ¹⁸FF-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.