Researchers at PSI have developed a brand new drug that would increase the survival possibilities of patients with metastatic prostate cancer. The drug is now being tested on patients within the PROGNOSTICS project. A research consortium consisting of the Paul Scherrer Institute, the University Hospital Basel and ETH Zurich is receiving two million Swiss francs in funding for this project.

In Switzerland, about 7100 men are diagnosed with prostate cancer yearly – some 1400 of them die since the tumor has already metastasized and now not responds to established treatments. Now there’s latest hope for these patients. Within the PROGNOSTICS (PeRsOnalised theraGNOstics of metaStaTIC proState cancer) project, teams led by Roger Schibli of PSI, Damian Wild of the University Hospital Basel and Nicola Aceto of ETH Zurich are testing a brand new radioactive drug which may be more promising than existing radiopharmaceuticals. The project will receive 2 million Swiss francs in funding, of which 1.7 million will come from the ETH Domain’s strategic focus area “Personalised Health and Related Technologies”. The study is scheduled to start out in July 2023, the clinical trial starts in 2024 and can run until the tip of 2025.

Hope for a 3rd of patients

About one-third of patients with metastatic prostate cancer don’t respond adequately to existing drugs: individual cancer cells can survive and form latest metastases. In the long run, latest radionuclides could help such patients. The Paul Scherrer Institute has been carrying out research right into a latest isotope – terbium-161 – and its therapeutic uses for around 10 years now. In laboratory tests, Cristina Müller’s research group at PSI’s Centre for Radiopharmaceutical Sciences has demonstrated that the brand new terbium-161 can treat tumors effectively. Within the context of PROGNOSTICS, this promising approach will now be tested on the University Hospital Basel on 30 patients for whom other therapies haven’t had the specified success.

Drugs of this sort – called radiopharmaceuticals – are radioactive substances which are injected into the bloodstream. The molecules are designed to connect themselves to the surface of tumor cells, like a key in a lock, but to not healthy cells. One end of the drug carries a radioactive atom that emits electrons (beta particles) during radioactive decay. These produce aggressive radicals contained in the tumor cell, i.e. highly reactive substances that may attack the cell’s genetic material and thus destroy it.

The consortium has now identified a possible reason why the radiopharmaceuticals currently used to treat prostate cancer don’t work in a 3rd of patients. The electrons emitted during radioactive decay deliver too small a dose to the smallest metastases or individual tumor cells, in order that these are in a position to survive.

Destroying tumor cells with even greater precision

In PROGNOSTICS, the partners at the moment are testing a drug that uses the isotope terbium-161. This isotope emits electrons with a wide selection of energies, including so-called conversion and Auger electrons. As a consequence of their low energies, these have a variety of just just a few micrometers. They release all of their energy in a cell or in a cluster of cells, making their destructive power more precisely targeted. The tumor cell is broken, isn’t any longer in a position to divide and eventually dies, stopping the formation of metastases.

Preclinical studies in mice at PSI have already shown that it is a promising approach. In PROGNOSTICS, the brand new drug will now be tested on the University Hospital Basel.

The project is benefiting from the event of isotopes at PSI’s large research facilities, led by Nicholas van der Meulen. PROGNOSTICS brings together scientists from the fields of physics, chemistry, biology, pharmacology and medicine who’re jointly developing the therapeutic approach from laboratory research to its application in patients. This just isn’t the primary time that an interdisciplinary project like this has been successfully implemented, as Schibli points out: “We’ve got shown up to now that we’re able to successfully conducting translational drug research.”

If PROGNOSTICS is successful and the anticipated goals are achieved, further, more extensive clinical trials are planned.