Kirkeby Emily K, Chyan Ming-Kuan, Diehl George, Wilbur D Scott, Li Yawen, Roberts Andrew G, Mastren Tara
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, UT, 84112, USA.
Department of Radiation Oncology, 616 N.E. Northlake Place, University of Washington, Seattle, WA, 98105, USA.
Appl Radiat Isot. 2023 Jan;191:110555. doi: 10.1016/j.apradiso.2022.110555. Epub 2022 Nov 10.
Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (Vizamyl) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. Our final compound [At]3'-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline.
阿尔茨海默病（AD）是一种晚期神经退行性疾病，其特征是淀粉样纤维、无定形聚集体的积累以及tau蛋白病变。几种依赖于各种生物学过程来减轻疾病负担的治疗方法，在治疗阿尔茨海默病方面大多无效。靶向α治疗（TAT）在癌症治疗中已显示出积极效果。苯并噻唑衍生物已成功证明可靶向这些斑块，并用于多种成像应用。一种这样的衍生物，氟代脱氧葡萄糖（Vizamyl）是一种经美国食品药品监督管理局（FDA）批准的用于AD相关斑块PET成像的诊断工具。我们报告了使用与硼酸前体分子的铜催化反应，用半衰期为7.2小时的α发射放射性核素砹对苯并噻唑衍生物进行放射性标记。我们的最终化合物[At]3'-At-PIB-OMe的放射化学产率为55%，并且发现在磷酸盐缓冲盐水中至少稳定3小时。
