INITIAL EVALUATION OF I-123 5-I-R91150, A SELECTIVE 5-HT2A LIGAND FORSINGLE-PHOTON EMISSION TOMOGRAPHY, IN HEALTHY-HUMAN SUBJECTS

The mapping of 5-HT2 receptors in the brain using functional imaging t echniques has been limited by a relative lack of selective radioligand s. Iodine-123 labelled -4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzam ide (I-123-5-I-R91150 or I-123-R93274) is a new ligand for single-phot on emission tomography (SPET), with high af finity and selectivity for 5-HT2A receptors. This study reports on preliminary I-123-5-I-R91150 SPET, whole body and blood distribution findings in five healthy hu ma n volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were a cquired with the brain-dedicated, single-slice multi-detector system S ME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT(2A) receptors. In contrast, ra dioligand binding in the frontal cortex increased steadily overtime, u p to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellu m activity ratios reached values of 1.4, and remained stable from appr oximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pa ttern of regional variation of binding compatible with the autoradiogr aphic data on the distribution of 5-HT2A receptors in humans (cerebral cortex>striatum>erebellum). These findings suggest that I-123-5-I-R91 150 may be used for the imaging of 5-HT2A receptors in the living huma n brain with SPET.