J Clin Invest. 2018 May 1;128(5):1727-1730. doi: 10.1172/JCI120388. Epub 2018 Apr 16.
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response. In this issue of the JCI, Makvandi and coworkers describe an approach to address this question using [18F]FluorThanatrace, an [18F]-labeled PARP-1 inhibitor, for PET. The tracer was taken up by patient tumor tissue and appeared to differentiate levels of PARP-1 expression; however, future studies should be aimed at determining if this tracer can be used to stratify patient response to PARPi therapy.
聚（ADP-核糖）聚合酶抑制剂（PARPi）是一种 DNA 损伤剂，可捕获 PARP-DNA 复合物并干扰 DNA 复制。三种 PARPi——奥拉帕利、尼拉帕利和鲁卡帕利——最近被 FDA 批准用于治疗乳腺癌和卵巢癌。这些 PARPi 以及另外两种（他拉唑帕利和 veliparib）正在评估其在治疗其他恶性肿瘤（包括前列腺癌）方面的潜力。尽管缺乏 PARP-1 会导致对 PARPi 的高度耐药，但尚未确定 PARP-1 的水平是否与肿瘤反应直接相关。在本期 JCI 中，Makvandi 及其同事描述了一种使用 [18F]FluorThanatrace（一种 [18F] 标记的 PARP-1 抑制剂）进行 PET 研究来解决这一问题的方法。该示踪剂被患者肿瘤组织摄取，似乎可以区分 PARP-1 表达水平；然而，未来的研究应该旨在确定这种示踪剂是否可用于分层患者对 PARPi 治疗的反应。
