Synthesis and Preliminary Evaluation of Piperidinyl and Pyrrolidinyl Iodobenzoates as Imaging Agents for Butyrylcholinesterase
Synthesis and Preliminary Evaluation of Piperidinyl and Pyrrolidinyl Iodobenzoates as Imaging Agents for Butyrylcholinesterase
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哌啶基和吡咯烷基碘苯甲酸酯的合成及丁酰胆碱酯酶显像剂的初步评价
DOI：
10.1007/s11307-010-0448-0
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发表时间：
2011
影响因子：
3.1
通讯作者：
S. Darvesh
中科院分区：
文献类型：
--
作者：
I. Macdonald;G. Reid;E. E. Joy;I. Pottie;I. Pottie;G. Matte;S. Burrell;G. Mawko;E. Martin;S. Darvesh;S. Darvesh
目的合成和评价与阿尔茨海默病（AD）神经斑块和神经原纤维缠结相关的丁基胆碱酯酶（BuChE）分子显像特异性药物。在本研究中，这些药物在正常大鼠模型上进行了测试。将放射性标记物的分布与已知BuChE在大鼠脑内的组织化学分布进行比较。合成十二苯甲酸酯，并通过分光光度法测定其作为BuChE的特异性底物。这些化合物从三丁基锡中间体转化为相应的123I酯，并被纯化用于大鼠模型的研究。获得全身动态扫描图像用于生物分布研究。获得脑切片的x线自显像，并与该模型系统中酶的组织化学分布进行比较。结果所研究的三种碘苯甲酸酯是BuChE的特异性底物。用123i标记的化合物进行的全身生物分布研究表明，这种化合物从体内迅速消失，而放射性则保留在头部区域。注射了这些标记化合物的动物的脑断层放射自显影显示，已知含有BuChE的大多数区域对应于放射性积聚区域。在组织化学研究中，BuChE特异性放射性标记碘苯甲酸盐进入大脑，通常标记已知具有BuChE活性的区域。这些分子可能代表了BuChE在活脑中的分子成像药物的发展新方向，特别是在AD中出现含BuChE的神经病理结构的区域。
PurposeThe purpose of this study is to synthesize and evaluate specific agents for molecular imaging of butyrylcholinesterase (BuChE), known to be associated with neuritic plaques and neurofibrillary tangles in Alzheimer’s disease (AD). In this study, these agents were tested in a normal rat model. The distribution of radiolabel was compared with known BuChE histochemical distribution in the rat brain.ProceduresIodobenzoate esters were synthesized and tested, through spectrophotometric analysis, as specific substrates for BuChE. These compounds were converted to the corresponding 123I esters from tributyltin intermediates and purified for studies in the rat model. Whole body dynamic scintigraphic images were obtained for biodistribution studies. Autoradiograms of brain sections were obtained and compared to histochemical distribution of the enzyme in this model system.ResultsThe three iodobenzoate esters studied were specific substrates for BuChE. Whole body biodistribution studies with 123I-labeled compounds showed rapid disappearance from the body while radioactivity was retained in the head region. Brain section autoradiography of animals injected with these labeled compounds indicated that most areas known to contain BuChE corresponded to areas of radioactivity accumulation.ConclusionBuChE-specific radiolabeled iodobenzoates enter the brain and, in general, label areas known to exhibit BuChE activity in histochemical studies. Such molecules may represent a new direction for the development of agents for the molecular imaging of BuChE in the living brain, especially in regions where BuChE-containing neuropathological structures appear in AD.
托烷和哌啶的 4-碘苯甲酰酯在多巴胺转运蛋白上的合成和配体结合研究。
影响因子：
7.3
作者：
Singh,S;Basmadjian,GP;Avor,KS;Pouw,B;Seale,TW
通讯作者：
Seale,TW
影响因子：
56.9
作者：
COYLE, JT;PRICE, DL;DELONG, MR
通讯作者：
DELONG, MR
影响因子：
2.1
作者：
GEULA, C;MESULAM, MM
通讯作者：
MESULAM, MM