SYNTHESIS AND EVALUATION OF 1'-[F-18]FLUOROMETOPROLOL AS A POTENTIAL TRACER FOR THE VISUALIZATION OF BETA-ADRENOCEPTORS WITH PET

(+/-)-1'-[F-18]Fluorometoprol 4 was prepared from desisopropylmetoprol ol and [F-18]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesul fonate) in 45% radiochemical yield (EOB, 40 min). Compound 4 shows in two in vitro assays a similar affinity at beta-adrenoceptors (about 0. 3 muM) as metoprolol 5, but with a slightly higher beta1/beta2-adrenoc eptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 sho wed almost no receptor-mediated uptake in the heart, probably because the affinity of (fluoro)metoprolol for the beta1-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [F-18] fluorinated beta1-adrenergic receptor binding ligands.