Serum levels of prostate-specific antigen (PSA) are widely used as a biomarker for prostate cancer, although they often do not distinguish between normal tissue and cancer and do not always accurately reflect clinical outcome. In order to overcome the fact that the small proportion of tumor-associated PSA that is released into circulation is rapidly and irreversibly converted to an inactive form, Ulmert and colleagues from Memorial Sloan-Kettering Cancer Center in New York developed a radiolabeled monoclonal antibody (89Zr–labeled 5A10) that selectively targets the initially produced active, “free” form of PSA.1 This selectivity potentially allows a more accurate, imaging-based clinical assessment of advanced prostate cancer.
Visualization of Lesions
The 89Zr–5A10 radiotracer was shown to localize in an androgen receptor–dependent manner in vivo in models of castration-resistant prostate cancer. The radiotracer was specifically taken up into tumor tissue of mice with subcutaneous PSA-positive prostate cancer xenografts and allowed measurement of changes in PSA production induced by testosterone or androgen receptor inhibition. Further, the radiotracer specifically localized to tumor-bearing mouse hind limbs, but not to sites of fracture and bone repair, thus overcoming the imitations of current bone scans that fail to distinguish between malignant and nonmalignant signals.
These findings indicate that a radiotracer that allows quantitation of androgen receptor–dependent changes in PSA expression levels at tumor lesions can selectively and noninvasively detect and permit visualization of primary and metastatic prostate tumors and measure responses to antiandrogen treatment. As stated by the investigators, “[T]he molecular imaging tool presented here could have near-term clinical impact, particularly because the dosimetry of other 89Zr-labeled monoclonal antibodies has been determined to be favorable for humans and will soon be examined in clinical trials.” ■
1. Ulmert D, Evans MJ, Holland JP, et al: Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen. Cancer Discov 2:320-327, 2012.