Brain Penetrant PARP Targeted PET Imaging Probes

资助父母补助金摘要 由于肿瘤细胞可以通过poly（ADP-2）介导的DNA修复在化疗/放疗中存活， 核糖）聚合酶-1（PARP-1）。PARP-1抑制剂（PARPis）单独使用或与化疗或 放射治疗，通过阻断PARP， 催化单个DNA修复。随着使用PARPis治疗胶质瘤的多项正在进行的临床试验， 通过定量PARP PET成像的基线PARP表达水平将提供预后信息， 指导未来精准治疗。然而，目前正在开发的PARP显像剂都不是脑 渗透剂，使大脑中PARP-1的可靠体内定量具有挑战性。在此，我们建议 评价几种BBB渗透剂PARP-1抑制剂作为潜在的PET显像剂。

ABSTRACT of the funded parent grant Because tumor cells can survive chemo/radiation therapies through DNA repairment mediated by poly(ADP- ribose) polymerase-1 (PARP-1). PARP-1 inhibitors (PARPis) alone, or in combination with chemotherapy or radiation therapy, have led to substantial gains in the overall survival of cancer patients, by obstructing PARP- catalyzed single DNA repair. With multiple ongoing clinical trials using PARPis to treat glioma, to quantify baseline PARP expression levels through quantitative PARP PET imaging will provide prognostic information to guide future precision treatment. However, none of the current PARP imaging agents under development is brain penetrant, making reliable in vivo quantification of PARP-1 in the brain challenging. Herein, we propose to evaluate several BBB penetrant PARP-1 inhibitors as potential PET imaging agents.