Description
W. Tinganelli1, O. Sokol1, O. Drayson1, W. Kai1, J.Jansen1, C.Vandevoorde1, Q. Huang2, J. Schuemann2, H. Paganetti2, D. Boscolo1, C. Schuy1, M. Durante1,3,4, U. Weber1,5.
1Biophysics Department. GSI Helmholtzzentrum für Schwerionenforschung GmbH. Darmstadt, Germany
2Department of Radiation Oncology. Massachusetts General Hospital & Harvard Medical School. Boston, USA
3Institute of Condensed Matter Physics, Technische Universität Darmstadt. Darmstadt, Germany
4Department of Physics ‘Ettore Pancini’, University Federico II. Naples, Italy
5Department LSE, Technische Hochschule Mittelhessen. Gießen, Germany
Our group was the first to demonstrate the feasibility of achieving a FLASH effect through ultra-high dose rate (UHDR) irradiation with a carbon ion (12C) beam, in both in vitro1 and in vivo2-3 experiments, and in both the entrance plateau region (EPR)2 and the spread-out Bragg peak (SOBP)3. Notably, a significant reduction in lung metastases was observed when comparing UHDR with conventional dose-rate (CDR) exposure in a murine model2.
In the present contribution, we will discuss our previous published studies as well as unpublished data from our most recent investigation into the potential of carbon ion UHDR irradiation combined with immune checkpoint inhibitors. Our results indicate no significant differences between UHDR and CDR irradiation in eliciting an immune response.
To conclude we will present very recent data on 12C-UHDR aimed at preserving cognitive function in C57BL/6 mice exposed to whole-brain irradiation in both the EPR and the SOBP. Preliminary findings indicate a protective effect and improved performance in the novel object recognition test at 2, 4 and 6 months after 12C-UHDR irradiation compared to CDR. In addition, skin toxicity assessments suggests that increased tissue oxygenation attenuates the FLASH effect. Overall, these results, supported by ongoing, more refined experiments, highlight the protective potential of carbon ion UHDR and provide new insights for optimizing high-LET radiotherapy with UHDR radiation.
References:
1) Tinganelli W, Sokol O, Quartieri M, Puspitasari A, Dokic I, Abdollahi A, Durante M, Haberer T, Debus J, Boscolo D, Voss B, Brons S, Schuy C, Horst F, Weber U. Ultra-high dose rate (FLASH) carbon ion irradiation: dosimetry and first cell experiments. Int J Radiat Oncol Biol Phys. 2022; S=360-3016(21)03129-1.
2) Tinganelli W, Weber U, Anggraeini P, Simoniello P, Abdollahi A, Oppermann J, Schuy C, Horst F, Helm A, Fournier C, Durante M. FLASH with carbon ions: Tumor control, normal tissue sparing, and distal metastasis in a mouse osteosarcoma model. Radiotherapy and Oncology. 2022; 175:185-190.
3) Tinganelli W, Puspitasari-Kokko A, Sokol O, Helm A, Simoniello P, Schuy C, Lerchl S, Eckert D, Oppermann J, Rehm A, Janssen S, Engel D, Moeller R, Romano R, Horst F, Boscolo D, Fournier C, Durante M, Weber U. FLASH Bragg-peak irradiation with a therapeutic carbon ion beam: first in vivo results. Int J Radiat Oncol Biol Phys. 2025;121(5):1282-1292.
