Synthesis, radiosynthesis, and biological evaluation of fluorine-18-labeled 2β-carbo(fluoroalkoxy)-3β-(3′-((Z)-2-haloethenyl)phenyl) nortropanes: Candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography

Article abstract of DOI:10.1021/jm800781a

The meta-vinylhalide fluoroalkyl ester nortropanes 1-4 were synthesized as ligands of the serotonin transporter (SERT) for use as positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that 1-4 have a high affinity for the SERT (K_i values = 0.3-0.4 nM) and are selective for the SERT over the dopamine and norepinephrine transporters (DAT and NET). MicroPET imaging in anesthetized cynomolgus monkeys with [¹⁸F]1-[¹⁸F]4 demonstrated that all four tracers behave similarly with peak uptake in the SERT-rich brain regions achieved after 45-55 min, followed by a steady washout. An awake monkey study was performed with [¹⁸F]1, which demonstrated that the uptake of [¹⁸F]1 was not influenced by anesthesia. Chase studies with the SERT ligand 15 displaced [¹⁸F]1-[¹⁸F]4, but chase studies with the DAT ligand 16 did not displace [¹⁸F]1-[¹⁸F]4 thus indicating that the tracers were binding specifically to the SERT.