High-resolution imaging of brain 5-HT1B receptors in the rhesus monkey using [11C]P943
High-resolution imaging of brain 5-HT1B receptors in the rhesus monkey using [11C]P943
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DOI：
10.1016/j.nucmedbio.2009.10.007
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Ding, Yu-Shin
中科院分区：
文献类型：
--
作者：
Nabulsi, Nabeel;Huang, Yiyun;Ding, Yu-Shin
血清素5-HT 1B受体调节血清素的释放，并参与各种疾病状态，包括抑郁症和精神分裂症。本研究的目的是评价一种高亲和力和高选择性拮抗剂[C-11]P943作为正电子发射断层扫描（PET）示踪剂用于5-HT 1B受体成像。[C-11]P943通过使用自动化模块用[C-11]碘甲烷或[C-11]三氟甲磺酸甲酯对前体进行N-甲基化来合成。平均放射化学产率约为。10%，放射化学纯度>99%，合成结束时的比活度为8.8 +/- 3.6 mCi/nmol（n=37）。PET成像在非人灵长类动物中进行，使用高分辨率研究断层扫描仪，采用推注/输注模式。结合电位（BPND）计算使用的平衡比例的区域小脑。示踪剂摄取在苍白球和枕叶皮质中最高，在基底节和丘脑中中等，在小脑中最低，这与已知的5-HT 1B受体的脑分布一致。以不同比活度输注示踪剂（通过添加不同量的未标记P943）以剂量依赖性方式降低BPND值，表明示踪剂结合的饱和性。采用选择性5-HT 1B/5-HT 1D拮抗剂GR 127935（2 mg/kg iv）进行的阻断研究导致各区域的BPND值降低42-95%;例如，在枕部区域，从0.71降至0.03，表明完全阻断。这些结果证明了[C-11]P943对5-HT 1B受体的饱和性和特异性，表明其适合作为人体5-HT 1B受体系统体内评价的PET放射性示踪剂。爱思唯尔公司出版
The serotonin 5-HT1B receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [C-11]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT1B receptor. [C-11]P943 was synthesized via N-methylation of the precursor with [C-11]methyl iodide or [C-11]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8 +/- 3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BPND) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT1B receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BPND values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT1B/5-HT1D antagonist, resulted in reduction of BPND values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [C-11]P943 for 5-HT1B receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT1B receptor system in humans. Published by Elsevier Inc.