I-123-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects

5-HT2A receptors have been implicated in the pathophysiology of mood disord ers and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity f or serotonin 5-HT2A receptors, (123)iodinated 4-amino-N-1-[3 -(4-fluorophen oxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (I-123-5-I-R9 1150), has been developed and has been shown to be suitable for single-phot on emission tomography (SPET) imaging. In this study the influence of age a nd gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of I-123-5-I-R91150 was administered to 26 normal vol unteers (13 females and 13 males) with an age range of 23-60 years. SPET im aging was performed with a triple-headed gamma camera. For semi-quantitativ e analysis, ratios of ligand binding in different regions of interest to th e binding in the cerebellum were calculated. Mean ratios of 1.7 were obtain ed. No gender difference was demonstrated. 5-HT2A binding was shown to decl ine with age. Over an age range of 40 years a reduction in ligand binding o f 42%+/-7% was found. These results are in agreement with in vitro and posi tron emission tomography findings of a decline in 5-HT2A receptor binding w ith age. The findings confirm the suitability of I-123-5-I-R91150 for SPET imaging of 5-HT2A receptors, and highlight the necessity for age-matched co ntrols in clinical studies.