Lipophilic metabolite of [123I]beta-CIT in human plasma may obstruct quantitation of the dopamine transporter.

I-123 or C-11 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) is a recently developed radioligand for the study of dopamine and serotonin reuptake sites in humans with single photon emission tomography (SPET) or positron emission tomography (PET). Determination of the radioligand metabolite pattern is fundamental for a quantitative analysis of radioligand binding. The metabolism of [123I]beta-CIT was determined by a gradient HPLC method in plasma samples of six human subjects. Two metabolites of [123I]beta-CIT were found, a polar and a lipophilic. At 4 h after [123I]beta-CIT injection the percentages of parent compound and polar and lipophilic metabolites were 23 +/- 3% (mean +/- SD), 33 +/- 11%, and 44 +/- 8%, respectively. The lipophilic metabolite might pass the blood-brain barrier and account for a fraction of free and nonspecifically bound radioactivity in brain. The existence of a lipophilic metabolite of [123I]beta-CIT may obstruct the use of simple ratio methods for quantitation of the dopamine transporter in brain.