(S,S)-1'-[F-18]FLUOROCARAZOLOL AND (S,R)-1'-[F-18]FLUOROCARAZOLOL, LIGANDS FOR THE VISUALIZATION OF PULMONARY BETA-ADRENERGIC RECEPTORS WITH PET

The beta-adrenoceptor antagonist carazolol has been labelled with fluo rine-18 in the isopropyl group via a reductive alkylation by [F-18]-fl uoroacetone of the corresponding (S)-desisopropyl compound according t o a known procedure. The introduction of fluorine in the isopropyl gro up creates a new stereogenic centre resulting in the formation of (S,S )- and (S,R)-1'-[F-18]fluorocarazolol, which were separated by HPLC. T issue distribution studies were performed in male Wistar rats. Both th e (S,S) and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mm ol) showed high uptake in lung and heart, which could be blocked by pr etreatment of the animals with (+/-)-propranolol. No significant diffe rences were observed between the biodistribution of the two diastereom ers. Metabolite analysis showed a rapid appearance of polar metabolite s in plasma, while at 60 min postinjection 92% and 82% of the total ra dioactivity in lung and heart was unmetabolized 1'-[F-18]fluorocarazol ol. In a PET study with male Wistar rats, the lungs were clearly visua lized and the pulmonary uptake was decreased after pretreatment of the animals with (+/-)-propranolol. The heart could not be visualized. Si milar results were obtained in PET-studies with lambs.