Cancers | |
DNA Repair Enzyme Poly(ADP-Ribose) Polymerase 1/2 (PARP1/2)-Targeted Nuclear Imaging and Radiotherapy | |
Michael Nader1  Anna Pacelli1  Nghia T. Nguyen2  Susanne Kossatz2  | |
[1] Department of Nuclear Medicine, University Hospital Essen, University of Duisburg–Essen, 45147 Essen, Germany;Department of Nuclear Medicine, University Hospital Klinikum Rechts der Isar and Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University Munich, 81675 Munich, Germany; | |
关键词: PARP1 inhibitors; DNA repair; PET imaging; radiotherapy; rucaparib; olaparib; | |
DOI : 10.3390/cancers14051129 | |
来源: DOAJ |
【 摘 要 】
Since it was discovered that many tumor types are vulnerable to inhibition of the DNA repair machinery, research towards efficient and selective inhibitors has accelerated. Amongst other enzymes, poly(ADP-ribose)-polymerase 1 (PARP1) was identified as a key player in this process, which resulted in the development of selective PARP inhibitors (PARPi) as anti-cancer drugs. Most small molecule PARPi’s exhibit high affinity for both PARP1 and PARP2. PARPi are under clinical investigation for mono- and combination therapy in several cancer types and five PARPi are now clinically approved. In parallel, radiolabeled PARPi have emerged for non-invasive imaging of PARP1 expression. PARP imaging agents have been suggested as companion diagnostics, patient selection, and treatment monitoring tools to improve the outcome of PARPi therapy, but also as stand-alone diagnostics. We give a comprehensive overview over the preclinical development of PARP imaging agents, which are mostly based on the PARPi olaparib, rucaparib, and recently also talazoparib. We also report on the current status of clinical translation, which involves a growing number of early phase trials. Additionally, this work provides an insight into promising approaches of PARP-targeted radiotherapy based on Auger and α-emitting isotopes. Furthermore, the review covers synthetic strategies for PARP-targeted imaging and therapy agents that are compatible with large scale production and clinical translation.
【 授权许可】
Unknown