Imaging of I2-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD)
Imaging of I2-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD)
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DOI：
10.1016/j.nucmedbio.2010.02.013
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发表时间：
2010-07-01
影响因子：
3.1
通讯作者：
Zhang, Ming-Rong
中科院分区：
文献类型：
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作者：
Kawamura, Kazunori;Naganawa, Mika;Zhang, Ming-Rong
前言：咪唑啉受体(IRS)是一类独特的受体，至少可分为I1R和I2R两种亚型。I(2)Rs与抑郁症、阿尔茨海默病、亨廷顿病和帕金森病有关。目前已合成了几种用于I(2)Rs的正电子发射断层扫描(PET)探针，但尚未对选择性PET探针用于I(2)Rs的成像进行评价。我们用C-11标记了选择性I2R配体2-(3-氟-4-甲苯基)-4，5-二氢-1H-咪唑(FTIMD)，并用2-(3-fluoro-[4-C-11]tolyl)-4，5-dihydro-1H-imidazole([C-11]FTIMD)进行了首次核磁共振成像。方法：在三(二亚甲基丙酮)二钯(0)和三(邻苯基)膦存在下，通过钯促进的交叉偶联反应制备了[C-11]FTIMD。用组织解剖法观察其在大鼠体内的生物分布。[C-11]FTIMD代谢物在脑组织和血浆中被检测。结果：[C-11]FTIMD的合成成功，具有合适的放射性。冷FTIMD和BU224联合注射0.1 mg/kg后15 mm和30 mm脑血比显著降低。在代谢物分析中，注射后30min脑内[C-11]FTIMD无变化，高达98%。在PET研究中，在I2R密度高的地区观察到高放射性水平。与对照组相比，1.0 mg/kg BU224可显著降低大鼠脑区放射性水平和V-T值。结论：[C-11]FTIMD在I2R密度较高的大鼠脑内具有与I(2)Rs的特异性结合。(C)2010 Elsevier Inc.保留所有权利。
Introduction: Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I1R and I2R). I(2)Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I(2)Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I(2)Rs by PET. We labeled a selective I2R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with C-11 and performed the first imaging of I(2)Rs by PET using 2-(3-fluoro-[4-C-11]tolyl)-4,5-dihydro-1H-imidazole ([C-11]FTIMD).Methods: [C-11]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [C-11]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [C-11]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated.Results: [C-11]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 mm after the injection. In metabolite analysis, unchanged [C-11]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I2R. The radioactivity levels and V-T values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control.Conclusion: [C-11]FTIMD showed specific binding to I(2)Rs in rat brains with a high density of I2R. (C) 2010 Elsevier Inc. All rights reserved.