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.