Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Cancer Biother Radiopharm. 2010 Oct;25(5):571-5. doi: 10.1089/cbr.2010.0794. Epub 2010 Sep 28.
The imaging of the distribution of β-amyloid plaques in the brain is becoming an important diagnostic modality in Alzheimer's disease. The present study reports the synthesis of novel benzothiazole derivatives. The final products were characterized by spectral techniques such as FTIR, (1)H NMR, and electrospray ionization-mass spectrometry. The structure-activity relationship of these benzothiazole derivatives is also reported. The K(i) values of these derivatives were evaluated by competitive binding assay studies. The analogs were labeled with (99m)Tc for the potential diagnostic imaging of Alzheimer's disease using stannous chloride as a reducing agent. The radiochemical stability was found to be ≥ 90% for both the compounds and they were stable for 10-12 hours in human serum. Biodistribution studies of the (99m)Tc complex in normal mice were performed after intravenous injection through the tail vein. The data showed high initial brain uptakes at 2 minutes (2.2% ± 0.1% ID/g), and brain activities washed out to 0.3% ± 0.02% ID/g at 6 hours. In conclusion, benzothiazole derivatives showed excellent binding affinities for β-amyloid aggregates and high initial brain uptakes in normal mice.
脑内β-淀粉样斑块分布的成像在阿尔茨海默病的诊断中变得越来越重要。本研究报告了新型苯并噻唑衍生物的合成。最终产物通过光谱技术如傅里叶变换红外光谱（FTIR）、（1）H NMR 和电喷雾电离质谱（ESI-MS）进行了表征。还报告了这些苯并噻唑衍生物的构效关系。通过竞争性结合测定研究评估了这些衍生物的 K(i) 值。使用氯化亚锡作为还原剂，将这些类似物标记为（99m）Tc，用于阿尔茨海默病的潜在诊断成像。两种化合物的放射化学稳定性均发现≥90%，在人血清中稳定 10-12 小时。通过尾静脉静脉内注射在正常小鼠中进行了（99m）Tc 络合物的生物分布研究。数据显示，在 2 分钟时（2.2%±0.1%ID/g）具有较高的初始脑摄取率，在 6 小时时脑摄取率降至 0.3%±0.02%ID/g。总之，苯并噻唑衍生物对β-淀粉样蛋白聚集物具有优异的结合亲和力，并在正常小鼠中具有较高的初始脑摄取率。
