Analyses of [F-18]altanserin bolus injection PET data. II: Consideration of radiolabeled metabolites in humans

Imaging serotonin-2A (5-HT2A) neuroreceptors with positron emission tomogra phy (PET) and [F-18]altanserin has been the focus of a series of PET studie s, as [F-18]altanserin is one of the most selective 5-HT2A antagonist radio tracers. Previous animal studies showed that radiolabeled metabolites (radi ometabolites) of [F-18]altanserin crossed the blood-brain barrier (BBB) to localize nonspecifically in brain, consistent with a constant radioactivity "background." In this work, we evaluated human bolus injection [F-18]altan serin PET data with detailed consideration of the impact of BBB-permeable m etabolites on the specific binding parameters. Data were quantified using e ither single (parent radiotracer), dual (parent radiotracer and radiometabo lites), or no arterial input function(s) (cerebellum as reference tissue in put function). A step-gradient high-performance liquid chromatography (HPLC ) analysis provided distinct separation of [F-18]altanserin and four radiol abeled components in plasma. After [F-18]altanserin injection, the step-gra dient data showed that the major BBB-permeable radiometabolites approached constant levels in plasma (>50 min), consistent with a constant metabolite "background." The single-input Logan graphical results were highly correlat ed with the dual-input results and its bias was fairly constant across regi ons and subjects, as similarly observed for a nongraphical reference tissue method. The most comprehensive and quantitatively valid analysis for bolus [F-18]altanserin PET data was the dual-input method that specifically acco unted for BBB-permeable metabolites, although the Logan analysis was prefer red because it provided a good compromise between validity, sensitivity, an d reliability of implementation. Further study is needed to better understa nd how the cerebellar kinetics of [F-18] altanserin and its radiometabolite s impact the reference tissue measures. Synapse 41:11-21, 2001, (C) 2001 Wi ley-Liss, Inc.