American Association for Cancer Research
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Supplemental materials and methods from A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy

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journal contribution
posted on 2023-03-31, 00:05 authored by Mehran Makvandi, Kuiying Xu, Brian P. Lieberman, Redmond-Craig Anderson, Samuel Sander Effron, Harrison D. Winters, Chenbo Zeng, Elizabeth S. McDonald, Daniel A. Pryma, Roger A. Greenberg, Robert H. Mach

Supplemental material and methods.




Basser Center for BRCA, and the K12 Abramson Cancer Paul Calabresi Career Development program



Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [125I]KX1 as a PARP-1–selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo. The pharmacologic properties of the PARP radiotracer [125I]KX1 was characterized in multiple cell lines where single-agent sensitivity was correlated with [125I]KX1 binding to PARP-1. In vivo evaluation of [125I]KX1 verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [125I]KX1 correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516–24. ©2016 AACR.