Experimental radiobiology of ion beams

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In treatment planning, the increased effectiveness of ion beams is considered by the relative biological effectiveness (RBE). As the RBE depends on ion species, linear energy transfer (LET), dose as well as on various biological factors, it is calculated by biomathematical models. These models were initially developed based on in vitro data but need to be further validated in vivo. Our group performs systematic dose response studies at the Heidelberg Ion Beam Therapy Center (HIT) to determine preclinical RBE-values in normal tissues and tumors as a function of the most important physical and biological parameters. For preclinical normal tissue, the RBE is determined at different positions within a 6 cm spread-out Bragg peak (SOBP) using different dose levels and ion species. The results are used to benchmark predictions of clinically applied RBE-models. For preclinical tumors, the impact of hypoxia, tumor differentiation and tumor growth on local tumor control is determined. These experiments are supported by imaging studies to identify predictive parameters for normal tissue and tumor response. Further investigations on the histological and molecular level are performed to identify the mechanisms.

• Hintz L., Glowa C., Saager M., Euler-Lange R., Peschke P., Brons S., Grün R., Scholz M., Mein S., Mairani A., Debus J., Karger C.P.: Relative biological effectiveness of single and split helium ion doses in the rat spinal cord increases strongly with linear energy transfer. Radiotherapy and Oncology 170, 224-230, 2022 https://www.sciencedirect.com/science/article/abs/pii/S0167814022001554?via%3Dihub

• Glowa C., Peschke P., Brons S., Debus J., Karger C.P.: Effectiveness of fractionated carbon ion treatments in three rat prostate tumors differing in growth rate, differentiation and hypoxia. Radiotherapy and Oncology, 158, 131-137, 2021 https://doi.org/10.1016/j.radonc.2021.01.038

• Bendinger A.L., Peschke P., Peter J., Debus J., Karger C.P., Glowa C.: High doses of photons and carbon ions comparably increase vascular permeability in R3327-HI prostate tumors: a dynamic contrast-enhanced MRI study. Radiation Research 194, 465–475, 2020 https://meridian.allenpress.com/radiation-research/article/194/5/465/445869/High-Doses-of-Photons-and-Carbon-Ions-Comparably

• Bendinger A.L., Seyler L., Saager M., Debus C., Peschke P., Komljenovic D., Debus J., Peter J., Floca R.O., Karger C.P., Glowa C.: Impact of single dose photons and carbon ions on perfusion and vascular permeability: A dynamic contrast-enhanced MRI pilot study in the anaplastic rat prostate tumor R3327-AT1. Radiation Research 193, 34-45, 2020 https://meridian.allenpress.com/radiation-research/article/193/1/34/434559/Impact-of-Single-Dose-Photons-and-Carbon-Ions-on

• Saager M., Glowa C., Peschke P., Brons S., Grün R., Scholz M., Debus J., Karger C.P.: Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model. Radiation Oncology 15, 6, 2020 https://ro-journal.biomedcentral.com/articles/10.1186/s13014-019-1439-1

• Bendinger A.L., Glowa C., Peter J., Karger C.P.: Photoacoustic imaging to assess pixel-based sO2-distributions in experimental prostate tumors. Journal of Biomedical Optics 23, 036009, 2018 https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-23/issue-03/036009/Photoacoustic-imaging-to-assess-pixel-based-sO2-distributions-in-experimental/10.1117/1.JBO.23.3.036009.full

• Saager M., Peschke P., Brons S., Debus J., Karger C.P.: Determination of the proton RBE in the rat spinal cord: Is there an increase towards the end of the spread-out Bragg peak? Radiotherapy and Oncology 128, 115–120, 2018 https://www.sciencedirect.com/science/article/pii/S0167814018301348?via%3Dihub

• Mena-Romano P., Cheng C., Glowa C., Peschke P., Pan L., Haberkorn U., Dimitrakopoulou-Strauss A., Karger C.P.: Measurement of hypoxia-related parameters in three sublines of a rat prostate carcinoma using dynamic 18F-FMISO-PET-CT and quantitative histology. American Journal of Nuclear Medicine and Molecular Imaging 5, 348-362, 2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529589/

• Karger C.P., Debus J., Peschke P., Münter M.W., Heiland S., Hartmann G.H.: Dose-response curves for late functional changes in the normal rat brain after single carbon-ion doses evaluated by magnetic resonance imaging: influence of follow-up time and calculation of relative biological effectiveness. Radiation Research 158, 545-555, 2002 https://meridian.allenpress.com/radiation-research/article/158/5/545/331844/Dose-Response-Curves-for-Late-Functional-Changes

• Karger C.P., Glowa C., Peschke P. Kraft-Weyrather W.: The RBE in ion beam radiotherapy: From experimental studies to clinical application. Zeitschrift für Medizinische Physik 31, 105-121, 2021 https://doi.org/10.1016/j.zemedi.2020.12.001

• Sørensen B.S., Pawelke J., Bauer J., Burnet N.G., Dasu A., Høyer M., Karger C.P., Krause M., Schwarz M., Underwood T.S.A., Wagenaar D., Whitfield G.A., Lühr A.: Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy? Radiotherapy and Oncology 163,177-184, 2021 https://www.sciencedirect.com/science/article/pii/S0167814021067104?via%3Dihub

• Fossati P., Matsufuji N., Kamada T., Karger C.P.: Radiobiological issues in prospective carbon ion therapy trials. Medical Physics 45, e1096-e1110, 2018 https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/mp.12506

• Verhaegen F., Dubois L., Gianolini S., Hill M.A., Karger C.P., Lauber K., Prise K.M., Sarrut D., Thorwarth D., Vanhove C., Vojnovic B., Weersink R., Wilkens J.J., Georg D.: ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges. Radiotherapy and Oncology 126, 471–478, 2018 https://www.sciencedirect.com/science/article/pii/S0167814017327330?via%3Dihub

• Karger C.P., Peschke P.: RBE and related modeling in carbon-ion therapy. Physics in Medicine and Biology 63, 01TR02, 2017 https://iopscience.iop.org/article/10.1088/1361-6560/aa9102