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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.

Figure 4. RBE of carbon ions under oxic and hypoxic conditions and oxygen enhancement rations (OER) of photons and carbon ions in a rat prostate carcinoma. RBE and OER values refer to tumor control doses (TCD50) derived from dose response curves for the endpoint local tumor control after irradiation with photon or carbon ion irradiations under oxic or hypoxic conditions.
© Glowa et al. 2024a, CC BY 4.0 license

Selected publications (in chronological order)

  • Glowa C, Bendinger AL, Euler-Lange R, Peschke P, Brons S, Debus J, Karger CP. Irradiation with Carbon Ions Effectively Counteracts Hypoxia-related Radioresistance in a Rat Prostate Carcinoma. Int J Radiat Oncol Biol Phys. 2024a May 31:S0360-3016(24)00627-8.
    doi: 10.1016/j.ijrobp.2024.05.004.
  • Glowa C, Saager M, Hintz L, Euler-Lange R, Peschke P, Brons S, Scholz M, Mein S, Mairani A, Karger CP. Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions. Phys Imaging Radiat Oncol. 2024b Apr 20;30:100581.
    doi: 10.1016/j.phro.2024.100581.
  • Welzel T, Saager M, Peschke P, Debus J, Karger CP. Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study. Radiat Res. 2024 Jul 1;202(1):11-15.
    doi: 10.1667/RADE-23-00151.1.
  • Hintz L, Glowa C, Saager M, Euler-Lange R, Peschke P, Brons S, Grün R, Scholz M, Mein S, Mairani A, Debus J, Karger CP. Relative biological effectiveness of single and split helium ion doses in the rat spinal cord increases strongly with linear energy transfer. Radiother Oncol. 2022 May;170:224-230.
    doi: 10.1016/j.radonc.2022.03.017.
  • Glowa C, Peschke P, Brons S, Debus J, Karger CP. Effectiveness of fractionated carbon ion treatments in three rat prostate tumors differing in growth rate, differentiation and hypoxia. Radiother Oncol. 2021 May;158:131-137.
    doi: 10.1016/j.radonc.2021.01.038.
  • Bendinger AL, Peschke P, Peter J, Debus J, Karger CP, Glowa C. High Doses of Photons and Carbon Ions Comparably Increase Vascular Permeability in R3327-HI Prostate Tumors: A Dynamic Contrast-Enhanced MRI Study. Radiat Res. 2020 Nov 10;194(5):465-475.
    doi: 10.1667/RADE-20-00112.1.
  • Bendinger AL, Seyler L, Saager M, Debus C, Peschke P, Komljenovic D, Debus J, Peter J, Floca RO, Karger CP, 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. Radiat Res. 2020 Jan;193(1):34-45.
    doi: 10.1667/RR15459.1.
  • Saager M, Glowa C, Peschke P, Brons S, Grün R, Scholz M, Debus J, Karger CP. Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model. Radiat Oncol. 2020 Jan 3;15(1):6.
    doi: 10.1186/s13014-019-1439-1.
  • Bendinger AL, Glowa C, Peter J, Karger CP. Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors. J Biomed Opt. 2018 Mar;23(3):1-11.
    doi: 10.1117/1.JBO.23.3.036009.
  • Saager M, Peschke P, Brons S, Debus J, Karger CP. Determination of the proton RBE in the rat spinal cord: Is there an increase towards the end of the spread-out Bragg peak? Radiother Oncol. 2018 Jul;128(1):115-120.
    doi: 10.1016/j.radonc.2018.03.002.
  • Mena-Romano P, Cheng C, Glowa C, Peschke P, Pan L, Haberkorn U, Dimitrakopoulou-Strauss A, Karger CP. Measurement of hypoxia-related parameters in three sublines of a rat prostate carcinoma using dynamic (18)F-FMISO-Pet-Ct and quantitative histology. Am J Nucl Med Mol Imaging. 2015 Jun 15;5(4):348-62.
    https://pubmed.ncbi.nlm.nih.gov/26269773/
  • Karger CP, Debus J, Peschke P, Münter MW, Heiland S, Hartmann GH. Dose-response curves for late functional changes in the normal rat brain after single carbon-on doses evaluated by magnetic resonance imaging: influence of follow-up time and calculation of relative biological effectiveness. Radiat Res. 2002 Nov;158(5):545-55.
    doi: 10.1667/0033-7587(2002)158[0545:drcflf]2.0.co;2.

Reviews (in chronological order)

  • Karger CP, Glowa C, Peschke P, Kraft-Weyrather W. The RBE in ion beam radiotherapy: In vivo studies and clinical application. Z Med Phys. 2021 May;31(2):105-121.
    doi: 10.1016/j.zemedi.2020.12.001.
  • Sørensen BS, Pawelke J, Bauer J, Burnet NG, Dasu A, Høyer M, Karger CP, Krause M, Schwarz M, Underwood TSA, Wagenaar D, Whitfield GA, Lühr A. Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy? Radiother Oncol. 2021 Oct;163:177-184.
    doi: 10.1016/j.radonc.2021.08.016.
  • Fossati P, Matsufuji N, Kamada T, Karger CP. Radiobiological issues in prospective carbon ion therapy trials. Med Phys. 2018 Nov;45(11):e1096-e1110.
    doi: 10.1002/mp.12506.
  • Verhaegen F, Dubois L, Gianolini S, Hill MA, Karger CP, Lauber K, Prise KM, Sarrut D, Thorwarth D, Vanhove C, Vojnovic B, Weersink R, Wilkens JJ, Georg D. ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges. Radiother Oncol. 2018 Mar;126(3):471-478.
    doi: 10.1016/j.radonc.2017.11.016.

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