Tj. Degroot et al., SYNTHESIS AND EVALUATION OF 1'-[F-18]FLUOROMETOPROLOL AS A POTENTIAL TRACER FOR THE VISUALIZATION OF BETA-ADRENOCEPTORS WITH PET, Nuclear medicine and biology, 20(5), 1993, pp. 637-642
(+/-)-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.