A radiometabolite study of the serotonin transporter PET radioligand [11C]MADAM

摘要

Introduction: 11C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [11C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO2MADAM.In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. Methods: Comparative PET imaging studies in non-human primate brain with [11C]MADAM and [11C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [11C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET. Results: PET imaging studies in non-human primate brain using [11C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [11C]SOMADAM in non-human primate plasma was approximately 5% at 4min and 1% at 15min after [11C]MADAM injection. HPLC analysis of brain sample after [11C]MADAM injection to rats demonstrated that [11C]SOMADAM was not detected in the brain. Conclusions: 11C]SOMADAM is not superior over [11C]MADAM as a SERT PET radioligand. Nevertheless, [11C]SOMADAM has been identified as a minor labeled metabolite of [11C]MADAM measured in monkey plasma. [11C]SOMADAM was not detected in rat brain.