Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen

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

Research output: Contribution to journalArticlepeer-review

Abstract

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. SIGNIFICA NCE: 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.

Original languageEnglish (US)
Pages (from-to)320-327
Number of pages8
JournalCancer discovery
Volume2
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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