¹²³I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT_2A receptors: influence of age and gender in healthy subjects

Abstract.

5-HT_2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT_2A receptors, ¹²³iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of ¹²³I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23–60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT_2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42%±7% was found. These results are in agreement with in vitro and positron emission tomography findings of a decline in 5-HT_2A receptor binding with age. The findings confirm the suitability of ¹²³I-5-I-R91150 for SPET imaging of 5-HT_2A receptors, and highlight the necessity for age-matched controls in clinical studies.