Synthesis and biological evaluation of novel radioiodinated benzimidazole derivatives for imaging α-synuclein aggregates
Synthesis and biological evaluation of novel radioiodinated benzimidazole derivatives for imaging α-synuclein aggregates
复制标题
用于α-突触核蛋白聚集体成像的新型放射性碘化苯并咪唑衍生物的合成和生物学评价
DOI：
10.1016/j.bmc.2017.10.010
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Saji H
中科院分区：
文献类型：
--
作者：
Watanabe H;Ariyoshi T;Ozaki A;Ihara M;Ono M;Saji H
α-突触核蛋白（α-syn）聚集体常见于帕金森病（PD）、路易体痴呆（DLB）及其他一些疾病患者的大脑。因此，α-syn聚集物的体内成像将有助于药物开发、早期诊断和疾病状态监测。为了开发针对α-syn聚集体的成像探针，我们合成并评价了三种新型放射性碘化苯并咪唑（BI）衍生物对α-syn聚集体的选择性成像。在结合实验中，BI-2对α-syn聚集体的选择性结合亲和力在BI衍生物中最高。此外，BI-2在PD脑切片中清晰地染色路易体，但在AD脑切片中未标记老年斑。然而，在正常小鼠的生物分布研究中，[125I]BI-2未表现出高脑摄取（注射后2分钟0.56%ID/g）。BI衍生物还需要进一步的结构修饰，但BI支架可能是开发α-syn成像探针的一个有吸引力的候选者。
α-Synuclein (α-syn) aggregates are commonly found in the brains of patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and some other diseases. Therefore, in vivo imaging of α-syn aggregates would aid in drug development, early diagnosis, and monitoring of disease status. In order to develop imaging probes targeting α-syn aggregates, we synthesized and evaluated three novel radioiodinated benzimidazole (BI) derivatives for selective imaging of α-syn aggregates. In binding experiments, BI-2 exhibited the highest selective binding affinity for α-syn aggregates among the BI derivatives. In addition, BI-2 clearly stained Lewy bodies in PD brain sections, but did not label senile plaques deposited in AD brain sections. However, in the biodistribution study using normal mice, [125I]BI-2 did not demonstrate high brain uptake (0.56%ID/g at 2-min post-injection). Further structural modifications of the BI derivatives are needed, but the BI scaffold may be an attractive candidate for developing α-syn imaging probes.