Imaging Androgen Receptor Signaling with a Radiotracer Targeting Free Prostate-Specific Antigen

Department of Surgery, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Cancer Discovery (Impact Factor: 19.45). 04/2012; 2(4):320-7. DOI: 10.1158/2159-8290.CD-11-0316
Source: PubMed


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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    • "Of great interest is the fact that 89Zr-5A10 is suitable for the quantification of AR transcriptional activity in preclinical models of androgen independent models. Additionally, 89Zr-5A10 is colocalized in PSA- and AR-positive Pca models and quantitatively predicted response to antiandrogen therapy [25]. This radiotracer appears to preferentially target malignant tumor cells and therefore may become a more predictive imaging biomarker in prostate cancer [26]. "
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