Ortmeyer Christian Paul, Haufe Günter, Schwegmann Katrin, Hermann Sven, Schäfers Michael, Börgel Frederik, Wünsch Bernhard, Wagner Stefan, Hugenberg Verena
Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany; Organic Chemistry Institute, University of Münster, Corrensstr. 40, D-48149 Münster, Germany.
Organic Chemistry Institute, University of Münster, Corrensstr. 40, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany.
Bioorg Med Chem. 2017 Apr 1;25(7):2167-2176. doi: 10.1016/j.bmc.2017.02.033. Epub 2017 Feb 16.
BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective F-fluorination at the boron-core. Attached to a bioactive molecule and labeled with [F]fluorine, the resulting compounds are promising tracers for multimodal imaging in vivo and can be used for PET and fluorescence imaging. A BODIPY containing a phenyl and a hydroxy substituent on boron was synthesized and characterized. Fluorinated and hydroxy substituted dyes were coupled to an isatin-based caspase inhibitor via cycloaddition and the resulting compounds were evaluated in vitro in caspase inhibition assays. The metabolic stability and the formed metabolites were investigated by incubation with mouse liver microsomes and LC-MS analysis. Subsequently the fluorophores were labeled with [F]fluorine and an in vivo biodistribution study using dynamic PET was performed.
硼二吡咯亚甲基（BODIPYs）是一类荧光染料，具有高稳定性和量子产率。它们的特点是能够在硼核上进行选择性氟氟化。与生物活性分子相连并用[F]氟标记后，所得化合物有望成为体内多模态成像的示踪剂，可用于正电子发射断层扫描（PET）和荧光成像。合成并表征了一种在硼上含有苯基和羟基取代基的BODIPY。通过环加成反应将氟化和羟基取代的染料与基于异吲哚酮的半胱天冬酶抑制剂偶联，并在体外半胱天冬酶抑制试验中对所得化合物进行评估。通过与小鼠肝微粒体孵育和液相色谱-质谱（LC-MS）分析研究了代谢稳定性和形成的代谢物。随后用[F]氟对荧光团进行标记，并使用动态PET进行了体内生物分布研究。
