IN-VIVO SPECT IMAGING OF 5-HT1A RECEPTORS WITH [I-123] P-MPPI IN NONHUMAN-PRIMATES

Citation
Hf. Kung et al., IN-VIVO SPECT IMAGING OF 5-HT1A RECEPTORS WITH [I-123] P-MPPI IN NONHUMAN-PRIMATES, Synapse, 24(3), 1996, pp. 273-281
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0887-4476
Volume
24
Issue
3
Year of publication
1996
Pages
273 - 281
Database
ISI
SICI code
0887-4476(1996)24:3<273:ISIO5R>2.0.ZU;2-4
Abstract
The in vivo imaging of a novel iodinated phenylpiperazine derivative f or 5-HT1A receptors, [I-123]p-MPPI 2''-pyridinyl)-p-iodobenzamido-]eth yl-piperazine), using single photon emission computed tomography (SPEC T), was evaluated in nonhuman primates. After an i.v. injection, [I-12 3]p-MPPI penetrated the blood-brain barrier quickly and localized in b rain regions where 5-HT1A receptor density is high (hippocampus, front al cortex, cingulate gyrus, entorhinal cortex). Maximum ratio of hippo campus to cerebellum was 3 to 1 at 50 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5-HT1A receptor density, was blocked by a chasing dose of (+/-) 8-OH-D PAT (2 mg/kg, i.v.) or non-radioactive p-MPPI(1 mg/kg, i.v.), whereas the regional distribution of [(123)]p-MPPI was unaffected by treatment with non 5-HT1A agents, such as ketanserin. Ex vivo and in vitro auto radiographic studies using monkey brain further confirmed that the spe cific binding of [I-123]p-MPPI is associated with 5-HT1A receptor site s. However, the initial attempt at [I-123]p-MPPI human imaging studies did not display specific localization of 5-HT1A receptors. This discr epancy observed for [I-123]p-MPPI may be due to a dramatic difference in metabolic pathways between humans and monkeys. (C) 1996 Wiley-Liss, Inc.