Ph. Elsinga et al., (S,S)-1'-[F-18]FLUOROCARAZOLOL AND (S,R)-1'-[F-18]FLUOROCARAZOLOL, LIGANDS FOR THE VISUALIZATION OF PULMONARY BETA-ADRENERGIC RECEPTORS WITH PET, Nuclear medicine and biology, 23(2), 1996, pp. 159-167
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.