Dopamine D4 receptor antagonist 3-(4-[18F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one([18F]FMTP): Radiosynthesis and in vivo characterization in rats

We synthesized a novel 18F-labeled dopamine D4 receptor antagonist (Ki=4.3 nM), 3-(4-[18F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one ([18F]FMTP), which has exhibited high affinity and selectivity. Radiosyntheses were accomplished by the reaction of fluorine-18-labeled intermediate with 8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1) followed by HPLC purification. The overall radiochemical yield of the radiosynthesis was 19.5% (decay corrected), the specific radioactivity was about 110 GBq/μmol and the radiochemical purity was greater than 99%, the time of synthesis and purification was approximately 110 min. Tissue distribution studies of the [18F]FMTP in rats showed that the radioactivity in the brain was concentrated in frontal cortex and medulla, the region that has a high density of D4 receptors. Pre-treatment with nonradioactive FMTP (1.0 mg/kg) produced a significant reduction of radioactivity in all the regions. About 40% of total radioactivity in plasma and 100% in rat brain extract represented unchanged radioligand at 60 min after injection as determined by HPLC. These results indicate that [18F]FMTP have some specific binding to the D4 receptor.