Using a radiopharmaceutical production cyclotron for radiobiological research
The Laboratory for High Energy Physics and the Institute of Anatomy at the University of Bern are establishing a pre-clinical proton therapy research facility at the Bern University Hospital (Inselspital). The facility centers on the Bern Medical Cyclotron, an 18 MeV compact cyclotron designed for microampere-range beam currents for radioisotope production. The Bern Medical Cyclotron can be adapted as a highly accessible and customizable platform for pre-clinical proton therapy research, enabling advanced modalities such as ultra-high dose rate (FLASH) radiotherapy and spatially fractionated radiation therapy. Human keratinocytes (HaCaT) and mouse melanoma (B16-F10) cell lines were irradiated with 8.14(29) MeV protons at conventional dose rates and with 225 kV X-rays at doses from 0 to 8 Gy. Clonogenic survival assays were analyzed using the linear-quadratic model, and relative biological effectiveness values were derived by comparing the proton and X-ray doses required for 0.1 survival. Proton irradiation yielded steeper survival curves than X-rays, indicating higher cytotoxicity. B16-F10 cells were most sensitive, with a relative biological effectiveness of 1.34 at 0.1 survival, while HaCaT cells showed a relative biological effectiveness of 1.21. These results confirm enhanced proton effectiveness in cell killing and demonstrate that the Bern Medical Cyclotron provides a reliable platform for radiobiological studies. Establishing in vitro proton irradiation capability marks a key milestone toward developing a comprehensive pre-clinical radiobiology research facility in Bern. Ongoing upgrades will further refine dosimetry and proton delivery, paving the way for future FLASH and proton spatially fractionated radiation therapy studies.