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UNLABELLED: 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.

Original publication

DOI

10.1158/2159-8290.CD-11-0316

Type

Journal

Cancer Discov

Publication Date

04/2012

Volume

2

Pages

320 - 327

Keywords

Animals, Cell Line, Tumor, Disease Models, Animal, Humans, Male, Mice, Molecular Imaging, Orchiectomy, Positron-Emission Tomography, Prostate-Specific Antigen, Prostatic Neoplasms, Radioactive Tracers, Radioisotopes, Receptors, Androgen, Signal Transduction, Tomography, X-Ray Computed, Zirconium