WestCHEM, School of Chemistry , University of Glasgow , The Joseph Black Building , Glasgow G12 8QQ , U.K.
Wolfson Whol Cancer Research Centre, Institute of Cancer Sciences , University of Glasgow , Glasgow G61 1QH , U.K.
J Med Chem. 2018 May 10;61(9):4103-4114. doi: 10.1021/acs.jmedchem.8b00138. Epub 2018 Apr 19.
Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET-magnetic resonance imaging techniques. Results showed that [F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors over-expressing PARP. [F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging.
聚（ADP-核糖）聚合酶（PARP）参与 DNA 断裂的修复，并且在多种肿瘤中过度表达，这使得 PARP 成为正电子发射断层扫描（PET）和单光子发射计算机断层扫描成像的有吸引力的生物标志物。因此，在过去十年中，人们一直致力于开发针对 PARP 的核成像剂。在这里，我们报告了一种基于强效 PARP 抑制剂奥拉帕利（1）的 PET 示踪剂的发现。我们的候选 PET 示踪剂[F]20 被合成并作为一种潜在的 PARP PET 放射性示踪剂在携带皮下胶质母细胞瘤异种移植物的小鼠中进行了评估，使用了离体生物分布和 PET-磁共振成像技术。结果表明，[F]20 可以以良好的放射性产率生产，并表现出特异性的 PARP 结合，允许可视化过度表达 PARP 的肿瘤。因此，[F]20 是一种潜在的体内 PARP PET 成像候选放射性示踪剂。
