（131）I-CHIBA-1001 用于 α7 烟碱型乙酰胆碱受体的实验研究。
An experimental study on (131)I-CHIBA-1001: a radioligand for α7 nicotinic acetylcholine receptors.
机构信息
Department of Nuclear Medicine, Peking University First Hospital, West District, Beijing, China.
出版信息
PLoS One. 2013 Jul 30;8(7):e70188. doi: 10.1371/journal.pone.0070188. Print 2013.
OBJECTIVE
The α7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer's disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand (131)I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain.
METHOD
(131)I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of (131)I-CHIBA-1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of (131)I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain.
RESULT
The radiolabeling yield of (131)I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification. (131)I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully.
CONCLUSION
The CHIBA-1001 can be successfully radiolabeled with (131)I using the chloramine-T method. (131)I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors. (131)I-CHIBA-1001 can be a candidate for imagingα7 acetylcholine receptors, which will be of great value for the diagnosis and treatment of mental diseases.
目的
α7 烟碱型乙酰胆碱受体（nAChRs）在神经精神疾病（如阿尔茨海默病和抑郁症）的病理生理学中发挥着重要作用。然而，目前尚无合适的正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）放射性配体可用于脑内α7 nAChRs 的成像。本研究旨在合成一种新型的 SPECT 放射性配体（131）I-CHIBA-1001，用于全身生物分布研究和脑内α7 nAChRs 的体内成像。
方法
采用氯胺-T 法合成（131）I-CHIBA-1001。通过测试不同的反应时间和温度条件，以获得更好的放射性标记产率。采用薄层层析（TLC）和高效液相色谱（HPLC）系统分析（131）I-CHIBA-1001 的放射性标记产率和放射化学纯度。在 KM 小鼠注射（131）I-CHIBA-1001 后不同时间点进行全身生物分布研究。使用猴进行脑内 SPECT 成像。
结果
（131）I-CHIBA-1001 在 90∼95°C 下反应 1.5∼2.0 小时，放射性标记产率达到 96%。经 HPLC 纯化后，放射化学纯度达到 99%以上。（131）I-CHIBA-1001 在室温及 37°C 下于生理盐水和新鲜人血清中均高度稳定。脑内 15、30 和 60 分钟的生物分布数据分别为 11.05±1.04%ID/g、8.8±0.04%ID/g 和 6.28±1.13%ID/g。在实验性 SPECT 成像中，放射性示踪剂在脑区的分布与猴脑内α7 nAChRs 的分布相平行。此外，在阻断 SPECT 成像研究中，选择性α7 nAChR 激动剂 SSR180711 成功阻断了脑内放射性摄取。
结论
采用氯胺-T 法可成功标记 CHIBA-1001 与（131）I。（131）I-CHIBA-1001 可成功积聚在猴脑中并对α7 乙酰胆碱受体进行成像。（131）I-CHIBA-1001 可作为成像α7 乙酰胆碱受体的候选药物，这对于精神疾病的诊断和治疗将具有重要价值。
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