Kung H F, Frederick D, Kim H J, McElgin W, Kung M P, Mu M, Mozley P D, Vessotskie J M, Stevenson D A, Kushner S A, Zhuang Z P
Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA.
Synapse. 1996 Nov;24(3):273-81. doi: 10.1002/(SICI)1098-2396(199611)24:3<273::AID-SYN10>3.0.CO;2-Y.
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.
利用单光子发射计算机断层扫描（SPECT）对一种新型用于5-HT1A受体的碘化苯基哌嗪衍生物[123I]p-MPPI（4-(2'-甲氧基)-苯基-1-[2'-(n-2"-吡啶基)-对碘苯甲酰胺基]-乙基哌嗪）进行了非人灵长类动物体内成像评估。静脉注射后，[123I]p-MPPI迅速穿透血脑屏障并定位于5-HT1A受体密度高的脑区（海马体、额叶皮质、扣带回、内嗅皮质）。注射后50分钟时，海马体与小脑的最大比值为3比1。放射性配体在富含5-HT1A受体密度的海马体区域的特异性结合可被追加以（±）8-OH-DPAT（2mg/kg，静脉注射）或非放射性p-MPPI（1mg/kg，静脉注射）阻断，而[123I]p-MPPI的区域分布不受非5-HT1A药物（如酮色林）治疗的影响。使用猴脑进行的离体和体外放射自显影研究进一步证实，[123I]p-MPPI的特异性结合与5-HT1A受体位点相关。然而，[123I]p-MPPI人体成像研究的初步尝试未显示出5-HT1A受体的特异性定位。观察到的[123I]p-MPPI的这种差异可能是由于人类和猴子代谢途径的巨大差异所致。
