ABSTRACT
The beta-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in the isopropyl group via a reductive alkylation by [18F]-fluoroacetone of the corresponding (S)-desisopropyl compound according to a known procedure. The introduction of fluorine in the isopropyl group creates a new stereogenic centre resulting in the formation of (S,S)- and (S,R)-1'-[18F]fluorocarazolol, which were separated by HPLC. Tissue distribution studies were performed in male Wistar rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mmol) showed high uptake in lung and heart, which could be blocked by pretreatment of the animals with (+/-)-propranolol. No significant differences were observed between the biodistribution of the two diastereomers. Metabolite analysis showed a rapid appearance of polar metabolites in plasma, while at 60 min postinjection 92% and 82% of the total radioactivity in lung and heart was unmetabolized 1'-[18F]fluorocarazolol. In a PET-study with male Wistar rats, the lungs were clearly visualized and the pulmonary uptake was decreased after pretreatment of the animals with (+/-)-propranolol. The heart could not be visualized. Similar results were obtained in PET-studies with lambs.
Subject(s)
Adrenergic beta-Antagonists , Carbazoles/chemistry , Lung/metabolism , Propanolamines/chemistry , Receptors, Adrenergic, beta/metabolism , Adrenergic beta-Antagonists/chemical synthesis , Adrenergic beta-Antagonists/pharmacokinetics , Animals , Biotransformation , Brain/metabolism , Carbazoles/pharmacokinetics , Erythrocytes/metabolism , Fluorine Radioisotopes , Isotope Labeling , Ligands , Male , Myocardium/metabolism , Propanolamines/pharmacokinetics , Radioligand Assay , Rats , Rats, Wistar , Sheep , Stereoisomerism , Tissue Distribution , Tomography, Emission-ComputedABSTRACT
6 alpha-[18F]Fluoroprogesterone 3 was prepared by the BF3.Et2O-catalyzed reaction of progest-5 alpha, 6 alpha-epoxy-3,20-bisketal 1 and [18F]fluoride as a possible route for the in vivo visualization of progesterone receptors by PET. The radiochemical yield of 3 was 25% (EOB) and the sp. act. was 5 MBq/mumol (100 Ci/mol, EOS).
