Two F-18 radiochemistry methods to synthesize a promising transient receptor potential canonical 5 (TRPC5) radioligand

•The synthesis of the first fluorine-18 labeled radiotracer [¹⁸F]TZ78141 that targets TRPC5 channel was successfully completed.•Two complementary radiosynthetic approaches were performed.•Preliminary in vivo evaluation in nonhuman primate demonstrated [18F]TZ78141 as a promising radiotracer for imaging TRPC5. TRPC5 is a member of the mammalian transient receptor potential (TRP) channel superfamily and it has been implicated in various physiological and pathological mechanisms of neurological and psychiatric diseases. Fluorine-18 is one of the most widely used radionuclides for PET imaging due to its favorable chemical characteristics and nuclear-physical properties. Herein, we describe two complementary radiosynthetic approaches and preliminary in vivo evaluation for [18F]TZ78141 as a novel and promising fluorine-18 labeled radiotracer for imaging TRPC5. The latter strategy employed a ruthenium-mediated radiofluorination method, facilitating the rapid synthesis of the desired radiotracer with substantial advantages in simplicity and efficiency. [Display omitted]