Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and within the neovasculature of other solid tumors. The non-prostatic expression of PSMA has been reported exclusively within the neovasculature endothelial cells of non-prostate cancers, however, there are few reports on PSMA expression on epithelial cells. Herein we describe PSMA expression in non-prostatic epithelial cells and characterize the potential of PSMA-binding agents to non-invasively detect that expression. Methods. PSMA expression data was extracted from publicly available genomic databases. Genomic data was experimentally validated for PSMA expression, by quantitative RT-PCR, flow cytometry and western blotting, in several non-prostatic cell lines and xenografts of melanoma and small cell lung cancer (SCLC) origin. Feasibility of PSMA detection in those tumor models was further established using PSMA-based nuclear and optical imaging agents and by biodistribution, blocking, and ex vivo molecular characterization studies. Results. We discovered that a small percentage of non-prostatic cancer cell lines and tumors express PSMA. Importantly, PSMA expression was sufficiently high to image established melanoma and SCLC xenografts using PSMA-based nuclear and optical imaging agents. Conclusions. These results indicate that PSMA expression in non-prostatic tumors may not be limited to the endothelium but may also include solid tumor tissue of non-prostate cancers including melanoma and small cell lung cancer. Our observations indicate broader applicability of PSMA targeted imaging and therapeutics.
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