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Cancer Discov. 2012 Apr;2(4):320-7. doi: 10.1158/2159-8290.CD-11-0316. Epub 2012 Mar 31.

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

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1
Department of Surgery, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

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 (89)Zr-labeled 5A10, a novel radiotracer that targets "free" PSA. (89)Zr-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 (89)Zr-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.

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PMID:
22576209
PMCID:
PMC3351274
DOI:
10.1158/2159-8290.CD-11-0316
[Indexed for MEDLINE]
Free PMC Article
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