PSMA-617 can be used to irradiate prostate cancer cells from the inside

Scientists at the German Cancer Research Centre (DKFZ) have developed an agent, PSMA-617, which is capable of attaching specifically to prostate cancer cells.

This agent can be labelled with various radioactive substances. When chemically bound to a weakly radioactive diagnostic radionuclide, it can detect prostate tumours and their metastases in PET scans. If labelled with a strongly radioactive therapeutic radionuclide, PSMA-617 can specifically destroy cancer cells. A first clinical application of this radiopharmaceutical at Heidelberg University Hospital has now delivered promising results.

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 targeted therapies against prostate cancer,” explained biotechnologist Dr Matthias Eder of DKFZ.

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

PSMA-617 can be used to detect small secondary tumours in other organs

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

Alternatively, the researchers can also bind a therapeutic radionuclide called lutetium-177 to PSMA-617. This radiopharmaceutical is taken up by tumour cells that carry the PSMA target molecule and then 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.

Clinical trials evaluating PSMA-617 are planned

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

In addition, PET/CT images confirmed that metastases 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,” said Haberkorn.

“Other agents that target PSMA and can be coupled with strong or weak radiation emitters are already being developed,” explained Prof. Dr Klaus Kopka, a chemist and departmental head at DKFZ. “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 tumours and metastases and is stored well in cancer cells. As a result, prostate cancer can be irradiated from the inside, so to speak.”