title: In vivo SPECT imaging of 5-HT1A receptors with [123I]p-MPPI in nonhuman primates.
abstract: The in vivo imaging of a novel iodinated phenylpiperazine derivative for 5-HT1A receptors, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido-] ethyl-piperazine), using single photon emission computed tomography (SPECT), was evaluated in nonhuman primates. After an i.v. injection, [123I]p-MPPI penetrated the blood-brain barrier quickly and localized in brain regions where 5-HT1A receptor density is high (hippocampus, frontal cortex, cingulate gyrus, entorhinal cortex). Maximum ratio of hippocampus 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-DPAT (2 mg/kg, i.v.) or non-radioactive p-MPPI (1 mg/kg, i.v.), whereas the regional distribution of [123I]p-MPPI was unaffected by treatment with non 5-HT1A agents, such as ketanserin. Ex vivo and in vitro autoradiographic studies using monkey brain further confirmed that the specific binding of [123I]p-MPPI is associated with 5-HT1A receptor sites. However, the initial attempt at [123I]p-MPPI human imaging studies did not display specific localization of 5-HT1A receptors. This discrepancy observed for [123I]p-MPPI may be due to a dramatic difference in metabolic pathways between humans and monkeys.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: D
authors.initials: D
authors.lastname: Frederick
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: W
authors.initials: W
authors.lastname: McElgin
authors.forename: M P
authors.initials: MP
authors.lastname: Kung
authors.forename: M
authors.initials: M
authors.lastname: Mu
authors.forename: P D
authors.initials: PD
authors.lastname: Mozley
authors.forename: J M
authors.initials: JM
authors.lastname: Vessotskie
authors.forename: D A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: S A
authors.initials: SA
authors.lastname: Kushner
authors.forename: Z P
authors.initials: ZP
authors.lastname: Zhuang
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology*; D001923:Brain Chemistry / Q000187:drug effects; D007457:Iodine Radioisotopes; D008024:Ligands; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000631:Aminopyridines; D007457:Iodine Radioisotopes; D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine