Analyses of [F-18]altanserin bolus injection PET data. I: Consideration ofradiolabeled metabolites in baboons

Positron emission tomography (PET) has been used to study serotonin 2A (5-H T2A) receptor binding in human brain using the 5-HT2A antagonist, [F-18]alt anserin. Previous analyses of bolus injection [F-18]altanserin data provide d 5-HT2A specific binding measures that were highly correlated with the in vitro distribution of 5-HT2A receptors and reflected decreased binding afte r ketanserin (5-HT2A antagonist) administration. These observations were ma de in the presence of a nonspecific tissue component that was consistent wi th blood-brain barrier (BBB) passage of radiolabeled metabolites (radiometa bolites). In this work, we evaluated the in vivo kinetics of [18F]altanseri n and two major radiometabolites of [F-18]altanserin, focusing on the kinet ics of free and nonspecifically-bound radioactivity. PET studies were perfo rmed in baboons after the bolus injection of [F-18]altanserin or one of its major radiometabolites, either [F-18]altanserinol or [F-18]4-(4-fluorobenz oyl)piperidine, at baseline and after pharmacologic receptor blockade (bloc king data). The cerebellar and blocking data were analyzed using either sin gle (parent radiotracer) or dual (parent radiotracer and radiometabolites) input function methods. After bolus injection of either [F-18]altanserin me tabolite, radioactivity crossed the BBB and localized nonspecifically. The radiometabolites were found to contribute to nonspecific "background" radio activity that was similar in receptor-poor and receptor-rich regions. After bolus injection in baboons, two of the major radiometabolites of [F-18]alt anserin crossed the BBB and contributed to a fairly uniform background of n onspecific radioactivity. This uniformity suggests that conventional analys es are appropriate for human bolus injection [F-18]altanserin PET data, alt hough these methods may overestimate [F-18]altanserin nonspecific binding. Synapse 41:1-10, 2001. (C) 2001 Wiley-Liss, Inc.