Radiosynthesis of bromine-76 and iodine-123 labelled enantiomers of A-69024: Radioligands for dopamine D1 receptor studies using PET and SPECT

The racemic dopamine D1 receptor antagonist A-69024 was labelled with bromi ne-76 for studies using PET and with iodine-123 for SPECT. [Br-76]A-69024 w as prepared via electrophilic bromodestannylation with NH4 Br-76 Th, use of chloramine-T in acid media resulted in radiochemical yields of 70-80%. The racemic radioligand was purified by semi-preparative C-18 reverse-phase HP LC while the (+) and (-) enantiomers were separated and isolated using chir al HPLC. Average specific activities of 11 GBq/mu mol were obtained. In an analogous manner, 2-[I-123]A-69024 was prepared via. electrophilic iododest annylation with (NaI)-I-123 resulting in radiochemical yields of 65-70%. Ch iral HPLC gave the (+) and (-) enantiomers with specific activities of >74 GBq/mu mol. The chemical and enantiomeric purity of each enantiomer of both radioligands assessed by chiral HPLC was >98%. Radiochemical purities meas ured by radio-TLC were >98%. The average time of synthesis for both prepara tions was 70 minutes.