American Association for Cancer Research
21598290cd110316-sup-cd_11-0316_meth_t16_f15_1794k.pdf (1.75 MB)

Supplementary Tables 1-16, Figures 1-15 from Imaging Androgen Receptor Signaling with a Radiotracer Targeting Free Prostate-Specific Antigen

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journal contribution
posted on 2023-04-03, 20:24 authored by David Ulmert, Michael J. Evans, Jason P. Holland, Samuel L. Rice, John Wongvipat, Kim Pettersson, Per-Anders Abrahamsson, Peter T. Scardino, Steven M. Larson, Hans Lilja, Jason S. Lewis, Charles L. Sawyers

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Despite intense efforts to develop radiotracers to detect cancers or monitor treatment response, few are widely used as a result of challenges with demonstrating clear clinical use. We reasoned that a radiotracer targeting a validated clinical biomarker could more clearly assess the advantages of imaging cancer. The virtues and shortcomings of measuring secreted prostate-specific antigen (PSA), an androgen receptor (AR) target gene, in patients with prostate cancer are well documented, making it a logical candidate for assessing whether a radiotracer can reveal new (and useful) information beyond that conferred by serum PSA. Therefore, we developed 89Zr-labeled 5A10, a novel radiotracer that targets “free” PSA. 89Zr–5A10 localizes in an AR-dependent manner in vivo to models of castration-resistant prostate cancer, a disease state in which serum PSA may not reflect clinical outcomes. Finally, we demonstrate that 89Zr–5A10 can detect osseous prostate cancer lesions, a context where bone scans fail to discriminate malignant and nonmalignant signals.Significance: This report establishes that AR-dependent changes in PSA expression levels can be quantitatively measured at tumor lesions using a radiotracer that can be rapidly translated for human application and advances a new paradigm for radiotracer development that may more clearly highlight the unique virtues of an imaging biomarker. Cancer Discov; 2(4); 320–7. ©2012 AACR.Read the Commentary on this article by Herschman and Czernin, p. 301This article is highlighted in the In This Issue feature, p. 288