The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands

Abstract

No-carrier-added (NCA) R(+)-7-chloro-8-hydroxy-3-(3'-[18F]fluoropropyl)-1-phenyl-2,3,4,5- tetrahydro-3-benzazepine (2b) (an analog of dopamine D-1 receptor ligand SCH 23390), ethyl 8-fluoro-5,6-dihydro-5-(3'-fluoropropyl)-6-oxo-4H- imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (4b) and 3'-[18F]fluoropropyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (6b) (analogs of the benzodiazepine RO 15-1788) were synthesized by alkylation of the corresponding nor-compound with NCA 1-[18F]fluoro-3-iodopropane in 10-15% yield (EOB) in approximately 110 min and with a mass of 2-3 nmol. Compound 2 is less potent (approximately 12-14 times) than SCH 23390 in binding to rat striatal membranes in vitro. Compounds 2b, 4b and 6b exhibit no specific anatomical distribution to mouse brain. These results suggest that the substituent at position 3 of SCH 23390, and position 5 and carboxylate group of RO 15-1788 are critical determinants both of affinity and selectivity for receptor binding, and underscores the evaluation necessary when even minor changes (C1 to C3) are made in bioactive compounds.