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

摘要

We synthesized a novel F-18-labeled dopamine D-4 receptor antagonist (Ki = 4.3 nM), 3-(4-[F-18]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one ([F-18]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 110GBq/mu mol and the radiochemical purity was greater than 99%, the time of synthesis and purification was approximately I 10 min. Tissue distribution studies of the [F-18]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 D-4 receptors. Pre-treatment with nonradioactive FMTP (1.0mg/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 60min after injection as determined by HPLC. These results indicate that [F-18]FMTP have some specific binding to the D-4 receptor. (c) 2005 Elsevier Ltd. All rights reserved.