ANALYSIS OF THE METABOLITES OF [I-123] BETA-CIT IN PLASMA OF HUMAN AND NONHUMAN-PRIMATES

[I-123] beta-CIT is a single photon emission computed tomography (SPEC T) radioligand that has been used for in vivo studies of the dopamine and serotonin transporters. Two metabolite peaks of beta-CIT have been observed by high performance liquid chromatography (HPLC), but neithe r has been chemically identified. One major metabolite is clearly hydr ophilic. Previous reports have not agreed on the amount of the second metabolite and the extent to which it may cross the blood-brain barrie r. To clarify this controversy, we have studied beta-CIT metabolites u sing a protein precipitation method and an organic extraction method f ollowed by HPLC separation. Plasma from both human and nonhuman (rhesu s) primates was analyzed. Concentrations of the second metabolite were substantially lower in rhesus than in human for nearly equal parent c oncentrations. Furthermore, in rhesus the second metabolite is partial ly soluble in the organic solvent ethyl acetate, whereas in human it i s essentially insoluble. These observations account for the contradict ions in the literature. The hydrophilic nature of the human metabolite renders it unlikely that it crosses the blood-brain barrier in suffic ient quantities to interfere with the quantitative assessment of dopam ine transporter densities. (C) 1997 Wiley-Liss, Inc.