Researchers from the Radboudumc, together with UMC Utrecht and University of Bari Aldo Moro, are receiving a grant of 850,000 Euros from NWO for their PlatiBone research project. Two companies will additionally invest 200,000 Euros. The partners are jointly developing new drugs to treat bone metastases. These drugs combine diagnostics, chemotherapy and radiation.
Effective treatments for bone metastases are still scarce. For example, in prostate cancer, doctors use radioactive radium, which is absorbed by bone and irradiates bone tumors. But recent research shows that this radiation can also damage healthy bone, while only a small number of patients actually responds well to this treatment. Therefore, there is an urgent need for effective treatment of bone metastases.
Combination of chemo and radiation
Lead applicant for the PlatiBone project Sander Leeuwenburgh (Department of Dentistry) has been working for several years on the design of new drugs and biomaterials containing so-called bisphosphonates. "These are drugs that bind to calcium in the body and specifically accumulate in bones," he explains. "By coupling other substances to these bisphosphonates, they are targeted towards bones. Together with a collaborating lab in Italy, we developed compounds of bisphosphonates with platinum. The platinum causes damage to DNA in cells that divide quickly, such as cancer cells, and therefore acts as chemotherapy. If platinum is combined with bisphosphonate, it accumulates specifically in bone with high metabolic activity such as bone cancer, where it can release the platinum-based drugs that damage cancer cells."
During discussions with the Department of Medical Imaging, the idea emerged to use radioactive platinum instead of ordinary platinum. Co-applicant Sandra Heskamp explains the advantages: "Radioactive platinum (Pt-195m) is a gamma emitter which means that you can monitor if the drug is indeed taken up by bone metastases upon injection into the bloodstream. Furthermore, radioactive platinum emits so-called Auger radiation. So in addition to the effect of platinum itself, the radioactive particles also damage the DNA of the cancer cells, causing them to die."
In the Platibone project the researchers will test whether compounds consisting of bisphosphonates linked to radioactive platinum can effectively treat bone metastases. Leeuwenburgh: "Until recently I could never imagine we would be able to use radioactive platinum as a therapy for bone cancer, so the collaboration in this project is truly unique. This is a great example of multidisciplinary teamwork, where the active contributions of different teams really add value."
The first chemical compounds have already been prepared together with the University of Bari in Italy. The researchers will now test these drugs on models of prostate cancer and breast cancer, as these are common types of cancers that often spread to bones. But this technique may also be effective for bone metastases caused by other cancers. The Departments of Orthopedics of Radboudumc and UMC Utrecht are therefore actively involved to evaluate the possibility for clinical translation. UMC Utrecht will also develop new animal models, where bone containing tumor cells will be placed under the skin. The aim of these models is to rapidly advance basic research into clinical applications.
In addition to the various Dutch and Italian universities, two companies specialized in production of nuclear medicines participate in PlatiBone: Urenco and NRG. Urenco will supply raw materials to NRG as source for production of radioactive platinum. NRG will optimize this production method towards a product for clinical use in patients. “This project connects perfectly with another project already underway with NRG,” says Heskamp. “In this Fieldlab project we are developing new radioactive drugs with other UMCs. Hopefully the two projects can reinforce each other to such extent that we’ll have new drugs for treatment of bone metastases."
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