Synthesis and evaluation of 1'-[18F]fluorometoprolol as a potential tracer for the visualization of beta-adrenoceptors with PET.
(+/-)-1'-[18F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [18F]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-toluenesulfonate) in 45% radiochemical yield (EOB, 40 min). Compound 4 shows in two in vitro assays a similar affinity at beta-adrenoceptors (about 0.3 microM) as metoprolol 5, but with a slightly higher beta 1/beta 2-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart, probably because the affinity of (fluoro)metoprolol for the beta 1-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [18F]fluorinated beta 1-adrenergic receptor binding ligands.
PET Center, University of Groningen, University Hospital, The Netherlands.
T J
TJ
de Groot
A
A
van Waarde
P H
PH
Elsinga
G M
GM
Visser
O E
OE
Brodde
W
W
Vaalburg
D000818:Animals; D005069:Evaluation Studies as Topic; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D005462:Fluorine Radioisotopes; D011943:Receptors, Adrenergic, beta; C082884:1'-fluorometoprolol; D008790:Metoprolol