QUANTIFICATION OF THE BETA-ADRENOCEPTOR LIGAND S-1'[F-18]FLUOROCARAZOLOL IN PLASMA OF HUMANS, RATS AND SHEEP

Myocardial and pulmonary beta-adrenoceptors can be imaged with -yl-oxy )-3-[1-(fluoromethyl)ethyl]amino-2-propanol (S-1'-[F-18]fluorocarazolo l, I). Quantification of unmodified fluorocarazolol in plasma is neces sary for analysis of PET images in terms of receptor densities. We hav e determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C-18) 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 les s than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and h uman volunteers, respectively. Protein binding in sheep and human plas ma was determined by ultrafiltration. The fraction of total plasma rad ioactivity bound to protein and the fraction representing unmodified r adioligand were linearly correlated, suggesting that fluorocarazolol w as more than 70% protein-bound, whereas its metabolites showed negligi ble protein binding. Direct injection of plasma on an ISRP column seem s a convenient method for quantification of lipophilic radioligands su ch as fluorocarazolol.