title: Quantification of the beta-adrenoceptor ligand S-1'-[18F]fluorocarazolol in plasma of humans, rats and sheep.
abstract: Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.
authors: Positron Emission Tomography (PET) Center, University Hospital, Groningen, Netherlands.
authors: A
authors: A
authors: van Waarde
authors: T J
authors: TJ
authors: Visser
authors: H
authors: H
authors: Posthumus
authors: P H
authors: PH
authors: Elsinga
authors: R L
authors: RL
authors: Anthonio
authors: A M
authors: AM
authors: van Loenen-Weemaes
authors: G M
authors: GM
authors: Visser
authors: G C
authors: GC
authors: Beaufort-Krol
authors: A M
authors: AM
authors: Paans
authors: W
authors: W
authors: Vaalburg
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002227:Carbazoles / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000097:blood*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012756:Sheep; D014462:Ultrafiltration
chemical_list: D001798:Blood Proteins; D002227:Carbazoles; D005462:Fluorine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C089702:fluorocarazolol