New radioligand therapy aims to help patients with incurable prostate cancer

A Danish research team led by Francesco Sergi-Lindell (Rigshospitalet) aims to develop an innovative treatment for patients with advanced and incurable prostate cancer. Securing a “Frontier Grant” of 5 million DKK marks a significant stride forward in their endeavours to help this patient group, who currently faces limited treatment options.

Prostate cancer stands as the second-leading cause of cancer-related deaths among Danish men, resulting in approximately 1,200 fatalities annually. While many types of prostate cancer respond to treatments targeting the male sex hormone testosterone, a subset of patients develops an advanced stage known as metastatic castration-resistant prostate cancer (mCRPC) and have only a few treatment options, if any. At this stage, the cancer has spread to other parts of the body and no longer responds to traditional hormone therapies.

“The treatment of metastatic castration-resistant prostate cancer is currently ineffective. Surgery is not an option any longer, and chemotherapy usually results in substantial side effects that prevent effective treatment. Our project aims to develop an extremely precise treatment using a unique radionuclide - Astatine-211- which is an alpha particle emitter that is, at this stage, routinely produced only in Copenhagen and a few other places in the world,” says Sergi-Lindell.

The idea behind the project that Sergi-Lindell is now further pursuing with a Frontier Grant was originally developed in a collaboration between Prof. Andreas Kjær (Rigshospitalet/University of Copenhagen), Prof. Matthias Herth (University of Copenhagen), and Dr. Andreas I. Jensen (Technical University of Denmark).

Radionuclide therapy, also known as Radioligand Therapy (RLT), is considered a safe and effective method for treating various types of cancer. The process involves the patient receiving a molecule containing a radionuclide. This molecule binds to the cancer cells and destroys them by emitting radiation from the radionuclide. “Once the radionuclide is delivered to the cancer cell, it is destroyed very efficiently,” says Francesco Sergi-Lindell.

Alpha radiation trumps beta radiation

In the current market, there is a radionuclide for the treatment of prostate cancer that emits beta radiation. Unfortunately, many patients do not respond to this treatment. This has prompted the Danish research team to consider an alternative approach, opting to use alpha radiation instead, as this has been proven to be significantly more effective than beta radiation.

Alpha radiation kills cancer cells by causing DNA-double strand breaks. This stands in contrast to beta radiation, which primarily induces DNA-single-strand breaks. Additionally, alpha radiation has a short range, minimizing its impact on healthy tissue.

To achieve this objective, the research team plans to introduce a unique alpha-emitting radionuclide known as astatine-211. This radionuclide is relatively easy to produce, has a short half-life, and undergoes a straightforward decay process, preventing unnecessary radiation exposure to the body. “Astatine-211 is presumed to result in less toxicity to healthy tissue due to its unique decay properties. This aspect is fundamental for us and distinguishes this radionuclide from others,” says Sergi-Lindell.

Grand ambitions and potential towards other cancer types

The project also aims to identify the optimal molecule capable of ferrying the radionuclide to cancer cells, thereby killing them. Additionally, the molecule must be efficiently excreted from the body to avoid unwanted radiation damage to healthy tissue.

Francesco Sergi-Lindell looks forward to leading the project. He has many years of experience in the medical use of radiopharmaceuticals along with extensive experience in business development and launching new ventures.

“The team I am part of is incredible. I feel very privileged and have great confidence in the project’s success,” Sergi-Lindell says. He does not shy away from acknowledging the substantial ambitions and the multitude of possibilities that lie ahead, for instance exploring the use of alpha-radiation for treating other cancer types.