A Diagnostics & Imaging Week

ATLANTA – Cytogen (Princeton, New Jersey), at the annual American Urological Association (Linthicum, Maryland) meeting here, made a presentation of data demonstrating the expression of prostate-specific membrane antigen (PSMA) in cancer of the kidney.

In the study, independent investigators at the Cleveland Clinic (Cleveland) evaluated PSMA expression in normal kidneys and tissue samples from both benign and malignant renal lesions using a tissue microarray. Specimens from 60 normal kidneys and 99 renal neoplasms of various cell types were immunostained with the vascular endothelial marker CD34 and an antibody to PSMA.

PSMA expression in tumor-associated neovasculature was tested in triplicate and scored for staining intensity and percentage of vessels. PSMA was not expressed in any vascular structures of normal kidneys though it was detected in the brush border of proximal tubules.

In renal neoplasms, PSMA was only detected in the tumor neovasculature.

"PSMA represents an excellent target for prostate and potentially other cancers," said Warren D.W. Heston, PhD, director of the research program in prostate cancer at the Cleveland Clinic Foundation and one of the authors of the study. "In addition to being abundantly and preferentially expressed on the surface of prostate cancer cells, PSMA is also present on endothelial cells of new blood vessels that supply most other solid tumors. Our study results demonstrating the expression of PSMA in kidney cancer justify continued exploration of both imaging and therapeutic approaches that recognize this unique target."

Differential PSMA staining was noted among the various pathological types of lesions. PSMA staining was positive in 16 of 21 (76%) clear cell carcinomas, five of 16 (31%) of chromophobe renal cell carcinomas, zero of 20 papillary renal cell carcinomas, 10 of 19 (53%) oncocytomas, three of 14 (21%) transitional cell carcinomas, and zero of 19 angiomyolipomas.

Only clear cell carcinoma lesions demonstrated diffuse strong staining while weak or focal staining was noted in half of the oncocytomas, less than one-third of chromophobe renal cell carcinomas, one-fifth of the transitional cell carcinomas, and none of the specimens of papillary renal carcinoma or angiomyolipoma. Clear cell carcinoma is the most common type of malignant renal tumor and oncocytoma is a rare benign lesion.

"This data emphasizes the growing relevance of PSMA as a tumor marker and suggests that it may have wider application than just prostate cancer," noted Michael Manyak, MD, vice president of medical affairs for Cytogen. "These findings may provide a means to differentiate renal tumors and also a method to evaluate possible recurrence in patients who undergo renal ablative procedures or partial nephrectomy for malignancy."

Cytogen's Prostascint molecular imaging agent is the first and only commercial product targeting PSMA, the company said. It consists of a monoclonal antibody (7E11.C5.3) directed against PSMA that is linked to the imaging radioisotope Indium-111. By targeting PSMA, the Prostascint molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera.

Prostascint is indicated as a diagnostic imaging agent in newly diagnosed patients with biopsy-proven prostate cancer, thought to be clinically localized after standard diagnostic evaluation and who are thought to be at high risk for pelvic lymph node metastases.