Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA.
Department of Internal Medicine, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
Mol Imaging Biol. 2022 Dec;24(6):853-861. doi: 10.1007/s11307-022-01746-w. Epub 2022 Jun 14.
PARP inhibitor (PARPi) therapy is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) genomic aberrations. However, only a fraction of patients with BRCA1/2 mutations respond to PARPi therapy. In this pilot study, we assess PARP-1 expression in prostate cancer patients with and without HRR genomic alternations using a novel PARP-based imaging agent.
Nine advanced prostate cancer patients were studied with PET/CT and [F]FluorThanatrace (FTT), an analogue of the PARPi rucaparib. Images were analyzed using maximum standardized uptake values (SUV). PARP expression was assessed by immunohistochemistry (IHC) when feasible (n = 4).
We found great variability in FTT uptake (SUV range: 2.3-15.4). Patients with HRR mutations had a significantly higher SUV (p = 0.0379) than patients with non-HRR mutations although there was an overlap in FTT uptake between groups. Three patients without HRR and one with HRR mutations had similarly high PARP1 IHC expression.
FTT-PET/CT may serve as an alternate biomarker for PARP1 expression and a potential method for PARPi treatment selection.
聚腺苷二磷酸核糖聚合酶（PARP）抑制剂（PARPi）疗法已获批用于转移性去势抵抗性前列腺癌（mCRPC）和同源重组修复（HRR）基因组异常患者。然而，仅有一部分 BRCA1/2 突变患者对 PARPi 治疗有反应。在这项初步研究中，我们使用一种新型基于 PARP 的成像剂评估了具有和不具有 HRR 基因组改变的前列腺癌患者的 PARP-1 表达。
9 名晚期前列腺癌患者接受了 PET/CT 和[F]氟他拉嗪（FTT）检查，FTT 是 PARPi 芦卡帕利的类似物。使用最大标准化摄取值（SUV）分析图像。在可行的情况下（n=4），通过免疫组化（IHC）评估 PARP 表达。
我们发现 FTT 摄取的变异性很大（SUV 范围：2.3-15.4）。具有 HRR 突变的患者的 SUV 显著更高（p=0.0379），尽管两组之间存在 FTT 摄取的重叠。3 名无 HRR 突变和 1 名 HRR 突变的患者具有相似高的 PARP1 IHC 表达。
FTT-PET/CT 可能作为 PARP1 表达的替代生物标志物和 PARPi 治疗选择的潜在方法。
