Radiosynthesis of (S)-[18F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors

After a synthesis time of 130 min (S)-[18F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-[18F]T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-[18F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-[18F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET.