New approaches for tumor therapy: Key publication from ERC project BARB on radioactive ion beams published in Nature Physics

The research project “BARB – Biomedical Applications of Radioactive Ion Beams” funded by a prestigious ERC Advanced Grant to Professor Marco Durante, head of the Biophysics Department at the GSI Helmholtzzentrum für Schwerionenforschung, has reached an important milestone: the first treatment of an animal tumor with radioactive ion beams has been demonstrated and published in Nature Physics. The study marks a decisive step towards the further development of particle therapy and is based on intensive collaboration between different GSI departments and FAIR pillars and with the Ludwig-Maximilians-Universität in Munich (LMU), Department of Medical Physics, who contributes to the BARB project as Associated Partner with a team led by Professor Katia Parodi.

BARB and the recently published paper are centered on the forward-looking idea of using radioactive ion beams (RIB) for simultaneous treatment and imaging. This approach could significantly reduce what is known as range uncertainty—one of the greatest challenges in particle therapy. Even if the idea had been already proposed almost 50 years ago at the Lawrence Berkeley Laboratory, it became feasible only now thanks to the intense beams that can already be produced during the “FAIR Phase 0” experimental operation at GSI/FAIR. The work now presented demonstrates for the first time the feasibility and great potential of the concept under realistic conditions.

Professor Marco Durante explains: “Particle therapy is growing rapidly and is possibly the most effective and precise radiation therapy technique. However, its application is still limited by technical constraints such as inadequate image guidance. The new idea of using the same beam for treatment and for imaging during treatment could pave the way for even more precise and diversified applications. Improving accuracy is a key to expanding the applicability of particle therapy.” This could also allow for better treatment of metastases or tumors near critical structures and small targets in non-cancerous diseases, such as ventricular ablations for cardiac arrhythmias.

In their publication “Image-guided treatment of mouse tumors with radioactive ion beams,” the scientists report the successful treatment of a bone tumor (osteosarcoma) of a mouse using a radioactive carbon ion beam (11C, which emits a positron with a half-life of about 20 minutes). The tumor was located in the neck area near the spinal cord, a highly sensitive area where even deviations of a few millimeters in the beam range could lead to unintended dose deposition in the spine and thus damage to the spinal cord. The researchers were able to achieve complete and very precise tumor control with the highest radiation dose of 20 gray, without paralysis or other major neurological side effects.

A detector developed at LMU Munich plays a key role in BARB, enabling the precise localization of the ion beam within the body. An international and interdisciplinary team at Professor Katia Parodi's Chair of Medical Physics, in collaboration with Professor Taiga Yamaya's laboratory (QST-Chiba), has developed a high-resolution and highly sensitive in-beam positron emission tomography (PET) scanner for small animals. The system was originally developed as part of Professor Parodi’s ERC Consolidator Grant “SIRMIO — Small animal proton irradiator for research in molecular image-guided radiation-oncology” to monitor the radiation-induced activity of proton beams and has been further developed in recent years as part of the BARB project to monitor radioactive ion beam treatments in real time. “The BARB project marked an important milestone for the first in vivo application of advanced instrumentation that we have developed over the past years at LMU to open new frontiers in high-precision image-guided small animal radiation research,” comments the LMU project lead Katia Parodi.

“Our work focused on real-time in-beam PET data acquisition and image reconstruction. This contributed to the first successful demonstration of tumor control using image-guided radioactive ion beam therapy in mice,” says co-first author Giulio Lovatti, who analyzed the PET data of the “Nature Physics” paper as part of his doctoral thesis in physics at LMU.

“BARB impressively demonstrates how applied nuclear physics can provide direct impetus for medical applications,” says project manager Marco Durante. “The close collaboration between the GSI/FAIR research pillars APPA and NuSTAR, as well as external partners such as LMU Munich, is a successful model for future research projects.”

The main objective of BARB was to perform the first in vivo tumor treatment with radioactive ion beams and online range verification using PET. With the results now presented in the key publication in “Nature Physics”, a decisive step has been taken in this direction. “We conclude that image-guided particle therapy with exotic beams is feasible, safe, and effective,” the researchers report, looking to the future. Further short-lived isotopes will be investigated, which researchers hope will provide a stronger signal and faster feedback during treatment. “We plan to run these experiments at the fragment separator Super-FRS currently under construction at FAIR, which will boost the intensity of the secondary radioactive beams,” says BARB project leader Professor Marco Durante and summarizes: “Our preclinical results demonstrate the feasibility of RIB radiation therapy and thus point the way toward future clinical applications of radioactive ion beams.”

The last experiments of the BARB project were recently completed in May and are now being published in further high-impact scientific journals. The experience gained at BARB is also highly relevant to Professor Durante's new ERC-funded project entitled “Heavy Ion FLASH (HI-FLASH)”. For this project, the researcher recently received another of the European Research Council's prestigious ERC Advanced Grants.