Ambur Sankaranarayanan Ramya, Kossatz Susanne, Weber Wolfgang, Beheshti Mohsen, Morgenroth Agnieszka, Mottaghy Felix M
Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany.
Department of Nuclear Medicine, University Hospital Klinikum Rechts der Isar, Technical University Munich, 81675 Munich, Germany.
J Clin Med. 2020 Jul 6;9(7):2130. doi: 10.3390/jcm9072130.
The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCA breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast developed and approved in this past decade, determination of PARP1 expression might help to predict the response to PARP inhibitor treatment. This has the potential of improving prognosis and moving towards tailored therapy options and/or dosages. This review summarizes the recent pre-clinical advancements in imaging and theranostic PARP1 targeted tracers. To assess PARP1 levels, several imaging probes with fluorescent or beta/gamma emitting radionuclides have been proposed and three have advanced to ongoing clinical evaluation. Apart from its diagnostic value in detection of primary tumors as well as metastases, this shall also help in delivering therapeutic radionuclides to PARP1 overexpressing tumors. Henceforth nuclear medicine has now advanced towards conjugating theranostic radionuclides to PARP1 inhibitors. This paves the way for a future of PARP1-targeted theranostics and personalized therapy.
癌症治疗中新型治疗方法的核心范式是识别和靶向分子生物标志物。其中一个这样的靶点是核DNA修复酶聚（ADP核糖）聚合酶1（PARP1）。在某些癌症如遗传性乳腺癌和卵巢癌中对PARP抑制的敏感性导致其被用作一个靶点。PARP1在几种类型的癌症中过表达进一步引发了将其用作成像靶点的兴趣。虽然在过去十年中PARP1靶向抑制剂迅速发展并获批，但PARP1表达的测定可能有助于预测对PARP抑制剂治疗的反应。这有可能改善预后并朝着定制治疗方案和/或剂量发展。本综述总结了成像和治疗诊断PARP1靶向示踪剂最近的临床前进展。为了评估PARP1水平，已经提出了几种带有荧光或发射β/γ放射性核素的成像探针，其中三种已进入正在进行的临床评估。除了其在检测原发性肿瘤以及转移灶方面的诊断价值外，这也将有助于将治疗性放射性核素递送至PARP1过表达的肿瘤。因此，核医学现已朝着将治疗诊断放射性核素与PARP1抑制剂偶联的方向发展。这为PARP1靶向治疗诊断和个性化治疗的未来铺平了道路。
