title: Initial evaluation of 123I-5-I-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects.
abstract: The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-io do-2-methoxybenzamide (123I-5-I-R91150 or 123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary 123I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i. ). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT2A receptors in humans (cerebral cortex>striatum>cerebellum). These findings suggest that 123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET.
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, London, UK.
authors.forename: G F
authors.initials: GF
authors.lastname: Busatto
authors.forename: L S
authors.initials: LS
authors.lastname: Pilowsky
authors.forename: D C
authors.initials: DC
authors.lastname: Costa
authors.forename: J
authors.initials: J
authors.lastname: Mertens
authors.forename: D
authors.initials: D
authors.lastname: Terriere
authors.forename: P J
authors.initials: PJ
authors.lastname: Ell
authors.forename: R
authors.initials: R
authors.lastname: Mulligan
authors.forename: M J
authors.initials: MJ
authors.lastname: Travis
authors.forename: J E
authors.initials: JE
authors.lastname: Leysen
authors.forename: D
authors.initials: D
authors.lastname: Lui
authors.forename: S
authors.initials: S
authors.lastname: Gacinovic
authors.forename: W
authors.initials: W
authors.lastname: Waddington
authors.forename: A
authors.initials: A
authors.lastname: Lingford-Hughes
authors.forename: R W
authors.initials: RW
authors.lastname: Kerwin
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000032:analysis*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D010880:Piperidines; C105020:R 91150; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin