QUANTIFICATION OF AN C-11 LABELED BETA-ADRENOCEPTOR LIGAND, S-(-)CGP-12177, IN PLASMA OF HUMANS AND RATS

beta-Adrenoceptors in human lungs and heart can be imaged with the rad ioligand -[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1 ,3-dihydro -2H-benzimidazol-2-C-11-one (CGP 12177, [C-11]I). For quantification o f receptor density with compartment models by adjustment of rate const ants, an 'input function' is required which consists of the integral o f the concentration of unmodified ligand in arterial plasma over time. A discrepancy in the literature regarding metabolic stability of [C-1 1]I prompted us to study metabolism in rats by reversed-phase HPLC (RP -HPLC) of trichloroacetic acid extracts of arterial plasma after i.v. injection of [C-11]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also directly applied to an internal-surface reversed-phase (ISR P) column. In parallel experiments, tritiated [C-11]I was employed and methanol extracts of arterial plasma were analyzed by straight-phase TLC. The three methods were in excellent agreement. Unmodified [C-11]I decreased from > 98.5% (H-3) or > 99.9% (C-11) initially to 57 +/- 7% at 80 min post injection due to formation of two polar metabolites. U sing the RP-HPLC method, no metabolism was detectable in humans up to 30 min after injection of [C-11]I (1851 MBq). Deproteinization of plas ma with acetonitrile resulted in the formation of a radioactive specie s (artifact) which eluted immediately after the void volume in RP-HPLC and which could be mistakenly interpreted as a metabolite. Plasma pro tein binding was low (ca. 30%) in both humans and rats. Association of the radioligand to blood cells suggested that equilibrium between rec eptor-bound and free radioligand was reached within 15 min after high- specific-activity injections, but only after more than 30 min after lo w-specific-activity injections.