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New Discovery for Diagnosis and Treatment of Prostate Cancer

Small molecule irradiates cancer cells from within

Prostate-specific membrane antigen (PSMA) is a surface protein that is normally present on healthy prostate cells but is found at much higher levels on prostate cancer cells. It is barely found in the rest of the body. “Therefore, PSMA is an ideal target for diagnostic purposes as well as for targeted therapies against prostate cancer,” according to biotechnologist Dr. Matthias Eder of the German Cancer Research Center in Heidelberg.

Eder’s group has developed a small molecule (PSMA-617) that is capable of specifically attaching to PSMA and that can be labeled with radioactive substances (radionuclides).

When chemically bound to gallium-68, a weakly radioactive diagnostic radionuclide, PSMA-617 can be used to visualize even the smallest assemblies of prostate cancer cells in positron emission tomography (PET) scans. “In this way, physicians are able to detect small secondary tumors in other organs or closely monitor the response to therapy. Diagnostic approaches that have been used in the clinic so far have not come close to this sensitivity,” Eder said.

Alternatively, the researchers can also bind a therapeutic radionuclide called lutetium-177 to PSMA-617. This radiopharmaceutical is taken up by tumor cells that carry the PSMA target molecule and destroys these cells from the inside. This might be a promising treatment option, particularly in cases of hormone-resistant prostate carcinoma, which is very difficult to treat, according to Eder.

At Heidelberg University Hospital, a team led by nuclear medicine specialist Professor Uwe Haberkorn has used radioactively labeled PSMA-617 to treat patients with advanced prostate cancer. The physicians used therapeutic nuclides lutetium-177 and actinium-225. After treatment with the lutetium-labeled radiopharmaceutical, levels of prostate-specific antigen (PSA), a prostate cancer marker, fell sharply in 70% of cases; after treatment with the actinium-labeled radiopharmaceutical, this effect was observed in all of the patients.

In addition, PET and computed tomography images confirmed that metastatic tumors had shrunk or were no longer detectable. “The results were so promising that we plan to go ahead with a clinical trial as soon as possible to examine whether PSMA-617 is superior to other therapy methods,” Haberkorn said.

“Other agents that target PSMA and that can be coupled with strong or weak radiation emitters are already being developed,” explained chemist Professor Klaus Kopka. “However, only a few of these agents have turned out to be ideal. Most of them are too unstable, accumulate insufficiently in cancer cells, and wash out too slowly from healthy organs. By contrast, PSMA-617 accumulates in large quantities in tumors and metastases, and is stored well in cancer cells. As a result, prostate cancer can be irradiated from the inside, so to speak.”

Source: German Cancer Research Center; June 22, 2015.

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