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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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.

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NIH

DOE

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

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ARTICLE ABSTRACT

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.