(S,S)- and (S,R)-1'-[18F]fluorocarazolol, ligands for the visualization of pulmonary beta-adrenergic receptors with PET.
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.
Elsinga
P H
PH
Pet-Center, University Hospital, Groningen, Netherlands.
Vos
M G
MG
van Waarde
A
A
Braker
A H
AH
de Groot
T J
TJ
Anthonio
R L
RL
Weemaes
A A
AA
Brodde
O E
OE
Visser
G M
GM
Vaalburg
W
W
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011412:Propanolamines / Q000737:chemistry* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012756:Sheep; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005462:Fluorine Radioisotopes; D008024:Ligands; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C089702:fluorocarazolol