Altropane, a SPECT or PET imaging probe for dopamine neurons: II. distribution to dopamine‐rich regions of primate brain
Altropane, a SPECT or PET imaging probe for dopamine neurons: II. distribution to dopamine‐rich regions of primate brain
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Altropane，一种用于多巴胺神经元的 SPECT 或 PET 成像探针：II. 灵长类动物大脑中富含多巴胺的区域的分布
作者：
B. Madras;L. Gracz;P. Meltzer;A. Liang;D. Elmaleh;M. Kaufman;A. Fischman
大脑中的多巴胺转运蛋白几乎只位于多巴胺神经元上，是多巴胺神经元的有效窗口。大脑中转运蛋白的 SPECT 或 PET 成像需要具有适当药代动力学特性的选择性成像剂。我们之前报道过[125I]阿托烷（[125I]IACFT,2β-甲甲氧基-3β-(4-氟苯基)-n-(1-碘丙-1-en-3-基)去甲托烷）以高亲和力（Kd：5.33 nM）与多巴胺转运蛋白上的单个位点结合，并且对多巴胺比血清素转运蛋白具有选择性 在猴子纹状体的匀浆中。为了确定[125I]阿托烷的选择性结合是否反映在其脑分布中，通过冠状脑切片的定量放射自显影测定了松鼠猴（Saimiri sciureus）大脑中[125I]阿托烷的体外和离体分布。在体外，[125I]altropane (2 nM) 分布是离散的，主要在富含多巴胺的壳核、尾状核和伏核中可检测到。由此产生的壳核：小脑比例超过 120:1 (n = 3)。 [125I]altropane 与多巴胺转运蛋白的选择性体外结合，浓度接近其 Kd 值（Kd：5.33 nM，单个高亲和力位点），凸显了其适用于体外研究不同脑区域中多巴胺转运蛋白的密度。在猴子中进行离体放射自显影以确定[125I]阿托烷体外的脑分布是否可以预测其静脉内给药后的脑分布模式。静脉注射后 30 分钟，在尾壳核和伏核中检测到最高水平的[125I]阿托烷（0.3 nmol/kg），在小脑和皮质中检测到最低水平。壳核或尾状核：小脑比率为 7。静脉注射后 30 分钟内进行大脑 SPECT 成像。注射证实[123I]阿托烷快速且选择性地积累至纹状体。静脉注射 30 分钟内阿托烷与富含多巴胺的纹状体选择性结合。给药表明它特别适合多巴胺转运蛋白和相关多巴胺神经元的 SPECT 或 PET 成像。突触 29:105–115, 1998。© 1998 Wiley‐Liss, Inc.
The dopamine transporter in brain, localized almost exclusively on dopamine neurons, is an effective window on dopamine neurons. SPECT or PET imaging of the transporter in brain requires selective imaging agents that display appropriate pharmacokinetic properties. We previously reported that [125I]altropane ([125I]IACFT,2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐n‐ (1‐iodoprop‐1‐en‐3‐yl)nortropane) bound with high affinity (Kd: 5.33 nM) to a single site on the dopamine transporter and was selective for dopamine over the serotonin transporter in homogenates of monkey striatum. To determine whether the selective binding of [125I]altropane is reflected in its brain distribution, the in vitro and ex vivo distribution of [125I]altropane in squirrel monkey (Saimiri sciureus) brain was determined by quantitative autoradiography of coronal brain sections. In vitro, [125I]altropane (2 nM) distribution was discrete and was detectable primarily in the dopamine‐rich putamen, caudate nucleus, and nucleus accumbens. The resulting putamen:cerebellum ratio exceeded 120:1 (n = 3). The selective in vitro binding of [125I]altropane to the dopamine transporter, at concentrations approaching its Kd value (Kd: 5.33 nM, a single high affinity site), highlight its suitability for investigating the density of the dopamine transporter in various brain regions in vitro. Ex vivo autoradiography was conducted in monkeys to determine whether the brain distribution of [125I]altropane in vitro was predictive of its brain distribution pattern after intravenous administration. Thirty minutes after intravenous injection, highest levels of [125I]altropane (0.3 nmol/kg) were detected in the caudate‐putamen and nucleus accumbens and lowest levels in the cerebellum and cortex. The putamen or caudate:cerebellum ratio was 7. SPECT imaging of the brain within 30 min of i.v. injection confirmed the rapid and selective accumulation of [123I]altropane to the striatum. The selective binding of altropane to the dopamine‐rich striatum within 30 min of i.v. administration indicates that it is uniquely suited for SPECT or PET imaging of the dopamine transporter and associated dopamine neurons. Synapse 29:105–115, 1998. © 1998 Wiley‐Liss, Inc.
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DOI：
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