Positron emission tomography (PET) has been used to study serotonin 2A (5-HT2A) receptor binding in human brain using the 5-HT2A antagonist, [18F]altanserin. Previous analyses of bolus injection [18F]altanserin data provided 5-HT2A specific binding measures that were highly correlated with the in vitro distribution of 5-HT2A receptors and reflected decreased binding after ketanserin (5-HT2A antagonist) administration. These observations were made in the presence of a nonspecific tissue component that was consistent with blood-brain barrier (BBB) passage of radiolabeled metabolites (radiometabolites). In this work, we evaluated the in vivo kinetics of [18F]altanserin and two major radiometabolites of [18F]altanserin, focusing on the kinetics of free and nonspecifically-bound radioactivity. PET studies were performed in baboons after the bolus injection of [18F]altanserin or one of its major radiometabolites, either [18F]altanserinol or [18F]4-(4-fluorobenzoyl)piperidine, at baseline and after pharmacologic receptor blockade (blocking data). The cerebellar and blocking data were analyzed using either single (parent radiotracer) or dual (parent radiotracer and radiometabolites) input function methods. After bolus injection of either [18F]altanserin metabolite, radioactivity crossed the BBB and localized nonspecifically. The radiometabolites were found to contribute to nonspecific "background" radioactivity that was similar in receptor-poor and receptor-rich regions. After bolus injection in baboons, two of the major radiometabolites of [18F]altanserin crossed the BBB and contributed to a fairly uniform background of nonspecific radioactivity. This uniformity suggests that conventional analyses are appropriate for human bolus injection [18F]altanserin PET data, although these methods may overestimate [18F]altanserin nonspecific binding.
- Positron emission tomography (PET)
- Serotonin receptor
ASJC Scopus subject areas