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A proof of principle experiment for microbeam radiation therapy at the Munich compact light source

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Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

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  1. Anschel DJ, Romanelli P, Benveniste H, Foerster B, Kalef-Ezra J, Zhong Z, Dilmanian FA (2007) Evolution of a focal brain lesion produced by interlaced microplanar X-rays. Minim Invasive Neurosurg MIN 50:43–46. https://doi.org/10.1055/s-2007-976514

  2. Archer J, Li E, Petasecca M, Dipuglia A, Cameron M, Stevenson A, Hall C, Hausermann D, Rosenfeld A, Lerch M (2017) X-ray microbeam measurements with a high resolution scintillator fibre-optic dosimeter. Sci Rep 7:12450. https://doi.org/10.1038/s41598-017-12697-6

  3. Bartzsch S, Oelfke U (2017) Line focus X-ray tubes—a new concept to produce high brilliance X-rays. Phys Med Biol 62:8600–8615. https://doi.org/10.1088/1361-6560/aa910b

  4. Beyreuther E, Bruchner K, Krause M, Schmidt M, Szabo R, Pawelke J (2017) An optimized small animal tumour model for experimentation with low energy protons. PLoS One 12:e0177428. https://doi.org/10.1371/journal.pone.0177428

  5. Bouchet A, Lemasson B, Le Duc G, Maisin C, Bräuer-Krisch E, Siegbahn EA, Renaud L, Khalil E, Rémy C, Poillot C, Bravin A, Laissue JA, Barbier EL, Serduc R (2010) Preferential effect of synchrotron microbeam radiation therapy on intracerebral 9L gliosarcoma vascular networks international. J Radiat Oncol Biol Phys 78:1503–1512. https://doi.org/10.1016/j.ijrobp.2010.06.021

  6. Bouchet A, Serduc R, Laissue JA, Djonov V (2015) Effects of microbeam radiation therapy on normal and tumoral blood vessels. Phys Med 31:634–641. https://doi.org/10.1016/j.ejmp.2015.04.014

  7. Bouchet A, Brauer-Krisch E, Prezado Y, El Atifi M, Rogalev L, Le Clec’h C, Laissue JA, Pelletier L, Le Duc G (2016) Better efficacy of synchrotron spatially microfractionated radiation therapy than uniform radiation therapy on glioma. Int J Radiat Oncol Biol Phys 95:1485–1494. https://doi.org/10.1016/j.ijrobp.2016.03.040

  8. Burger K, Ilicic K, Dierolf M, Gunther B, Walsh DWM, Schmid E, Eggl E, Achterhold K, Gleich B, Combs SE, Molls M, Schmid TE, Pfeiffer F, Wilkens JJ (2017) Increased cell survival and cytogenetic integrity by spatial dose redistribution at a compact synchrotron X-ray source. PLoS One 12:e0186005. https://doi.org/10.1371/journal.pone.0186005

  9. Chtcheprov P, Burk L, Yuan H, Inscoe C, Ger R, Hadsell M, Lu J, Zhang L, Chang S, Zhou O (2014) Physiologically gated microbeam radiation using a field emission X-ray source array. Med Phys 41:081705. https://doi.org/10.1118/1.4886015

  10. Crosbie JC, Anderson RL, Rothkamm K, Restall CM, Cann L, Ruwanpura S, Meachem S, Yagi N, Svalbe I, Lewis RA, Williams BRG, Rogers PAW (2010) Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues. Int J Radiat Oncol Biol Phys 77:886–894. https://doi.org/10.1016/j.ijrobp.2010.01.035

  11. Dilmanian FA, Button TM, Le Duc G, Zhong N, Pena LA, Smith JA, Martinez SR, Bacarian T, Tammam J, Ren B, Farmer PM, Kalef-Ezra J, Micca PL, Nawrocky MM, Niederer JA, Recksiek FP, Fuchs A, Rosen EM (2002) Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy. Neurooncology 4:26–38

  12. Dilmanian FA, Zhong Z, Bacarian T, Benvenlste H, Romanelli P, Wang R, Welwart J, Yuasa T, Rosen EM, Anschel DJ (2006) Interlaced X-ray microplanar beams: a radiosurgery approach with clinical potential. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0603567103

  13. Dilmanian FA, Qu Y, Feinendegen LE, Pena LA, Bacarian T, Henn FA, Kalef-Ezra J, Liu S, Zhong Z, McDonald JW (2007) Tissue-sparing effect of X-ray microplanar beams particularly in the CNS: is a bystander effect involved? Exp Hematol 35:69–77. https://doi.org/10.1016/j.exphem.2007.01.014

  14. Dombrowsky AC, Schauer J, Sammer M, Blutke A, Walsh DWM, Schwarz B, Bartzsch S, Feuchtinger A, Reindl J, Combs SE, Dollinger G, Schmid TE (2019) acute skin damage and late radiation-induced fibrosis and inflammation in murine ears after high-dose irradiation. Cancers. https://doi.org/10.3390/cancers11050727

  15. Eggl E, Dierolf M, Achterhold K, Jud C, Gunther B, Braig E, Gleich B, Pfeiffer F (2016) The Munich compact light source: initial performance measures. J Synchrotron Radiat 23:1137–1142. https://doi.org/10.1107/s160057751600967x

  16. Fardone E, Pouyatos B, Bräuer-Krisch E, Bartzsch S, Mathieu H, Requardt H, Bucci D, Barbone G, Coan P, Battaglia G, Le Duc G, Bravin A, Romanelli P (2018) Synchrotron-generated microbeams induce hippocampal transections in rats. Sci Rep 8:184. https://doi.org/10.1038/s41598-017-18000-x

  17. Favaudon V, Caplier L, Monceau V, Pouzoulet F, Sayarath M, Fouillade C, Poupon MF, Brito I, Hupe P, Bourhis J, Hall J, Fontaine JJ, Vozenin MC (2014) Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med 6:245–293. https://doi.org/10.1126/scitranslmed.3008973

  18. Fernandez-Palomo C, Mothersill C, Bräuer-Krisch E, Laissue J, Seymour C, Schültke E (2015) γ-H2AX as a marker for dose deposition in the brain of Wistar rats after synchrotron microbeam radiation. PLoS One 10:e0119924. https://doi.org/10.1371/journal.pone.0119924

  19. Gil S, Sarun S, Biete A, Prezado Y, Sabés M (2011) Survival Analysis of F98 glioma rat cells following minibeam or broad-beam synchrotron radiation therapy. Radiat Oncol 6:1–9. https://doi.org/10.1186/1748-717x-6-37

  20. Girst S, Greubel C, Reindl J, Siebenwirth C, Zlobinskaya O, Walsh DW, Ilicic K, Aichler M, Walch A, Wilkens JJ, Multhoff G, Dollinger G, Schmid TE (2016) Proton minibeam radiation therapy reduces side effects in an in vivo mouse ear model. Int J Radiat Oncol Biol Phys 95:234–241. https://doi.org/10.1016/j.ijrobp.2015.10.020

  21. Griffin RJ, Koonce NA, Dings RP, Siegel E, Moros EG, Brauer-Krisch E, Corry PM (2012) Microbeam radiation therapy alters vascular architecture and tumor oxygenation and is enhanced by a galectin-1 targeted anti-angiogenic peptide. Radiat Res 177:804–812

  22. Hadsell M, Zhang J, Laganis P, Sprenger F, Shan J, Zhang L, Burk L, Yuan H, Chang S, Lu J, Zhou O (2013) A first generation compact microbeam radiation therapy system based on carbon nanotube X-ray technology. Appl Phys Lett 103:183505. https://doi.org/10.1063/1.4826587

  23. Ibahim MJ, Crosbie JC, Yang Y, Zaitseva M, Stevenson AW, Rogers PA, Paiva P (2014) An evaluation of dose equivalence between synchrotron microbeam radiation therapy and conventional broad beam radiation using clonogenic and cell impedance assays. PLoS One 9:e100547. https://doi.org/10.1371/journal.pone.0100547

  24. Jacquet M, Suortti P (2015) Radiation therapy at compact compton sources. Phys Med 31:596–600. https://doi.org/10.1016/j.ejmp.2015.02.010

  25. Joiner M, Van der Kogel A (2009) Basic clinical radiobiology, 4th edn. Hodder Education, London

  26. Kim JW, Lee DW, Choi WH, Jeon YR, Kim SH, Cho H, Lee EJ, Hong ZY, Lee WJ, Cho J (2013) Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation. J Radiat Res 54:823–831. https://doi.org/10.1093/jrr/rrt016

  27. Kinner A, Wu W, Staudt C, Iliakis G (2008) Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res 36:5678–5694. https://doi.org/10.1093/nar/gkn550

  28. Laissue JA, Geiser G, Spanne PO, Dilmanian FA, Gebbers JO, Geiser M, Wu XY, Makar MS, Micca PL, Nawrocky MM, Joel DD, Slatkin DN (1998) Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X-rays. Int J Cancer 78:654–660. https://doi.org/10.1002/(sici)1097-0215(19981123)78:5%3c654:aid-ijc21%3e3.0.co;2-l

  29. Oppelt M, Baumann M, Bergmann R, Beyreuther E, Brüchner K, Hartmann J, Karsch L, Krause M, Laschinsky L, Leßmann E, Nicolai M, Reuter M, Richter C, Sävert A, Schnell M, Schürer M, Woithe J, Kaluza M, Pawelke J (2015) Comparison study of in vivo dose response to laser-driven versus conventional electron beam. Radiat Environ Biophys 54:155–166. https://doi.org/10.1007/s00411-014-0582-1

  30. Prezado Y, Fois G, Le Duc G, Bravin A (2009) Gadolinium dose enhancement studies in microbeam radiation therapy. Med Phys 36:3568–3574. https://doi.org/10.1118/1.3166186

  31. Regnard P, Le Duc G, Brauer-Krisch E, Tropres I, Siegbahn EA, Kusak A, Clair C, Bernard H, Dallery D, Laissue JA, Bravin A (2008) Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar X-ray beams from a synchrotron: balance between curing and sparing. Phys Med Biol 53:861–878. https://doi.org/10.1088/0031-9155/53/4/003

  32. Sabatasso S, Laissue JA, Hlushchuk R, Graber W, Bravin A, Brauer-Krisch E, Corde S, Blattmann H, Gruber G, Djonov V (2011) Microbeam radiation-induced tissue damage depends on the stage of vascular maturation. Int J Radiat Oncol Biol Phys 80:1522–1532. https://doi.org/10.1016/j.ijrobp.2011.03.018

  33. Schleede S, Bech M, Achterhold K, Potdevin G, Gifford M, Loewen R, Limborg C, Ruth R, Pfeiffer F (2012a) Multimodal hard X-ray imaging of a mammography phantom at a compact synchrotron light source. J Synchrotron Radiat 19:525–529. https://doi.org/10.1107/s0909049512017682

  34. Schleede S, Meinel FG, Bech M, Herzen J, Achterhold K, Potdevin G, Malecki A, Adam-Neumair S, Thieme SF, Bamberg F, Nikolaou K, Bohla A, Yildirim AO, Loewen R, Gifford M, Ruth R, Eickelberg O, Reiser M, Pfeiffer F (2012b) Emphysema diagnosis using X-ray dark-field imaging at a laser-driven compact synchrotron light source. Proc Natl Acad Sci USA 109:17880–17885. https://doi.org/10.1073/pnas.1206684109

  35. Serduc R, Christen T, Laissue J, Farion R, Bouchet A, Sanden B, Segebarth C, Brauer-Krisch E, Le Duc G, Bravin A, Remy C, Barbier EL (2008) Brain tumor vessel response to synchrotron microbeam radiation therapy: a short-term in vivo study. Phys Med Biol 53:3609–3622. https://doi.org/10.1088/0031-9155/53/13/015

  36. Serduc R, Bouchet A, Brauer-Krisch E, Laissue JA, Spiga J, Sarun S, Bravin A, Fonta C, Renaud L, Boutonnat J, Siegbahn EA, Esteve F, Le Duc G (2009) Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose. Phys Med Biol 54:6711–6724. https://doi.org/10.1088/0031-9155/54/21/017

  37. Serduc R, Brauer-Krisch E, Siegbahn EA, Bouchet A, Pouyatos B, Carron R, Pannetier N, Renaud L, Berruyer G, Nemoz C, Brochard T, Remy C, Barbier EL, Bravin A, Le Duc G, Depaulis A, Esteve F, Laissue JA (2010) High-precision radiosurgical dose delivery by interlaced microbeam arrays of high-flux low-energy synchrotron X-rays. PLoS One 5:e9028. https://doi.org/10.1371/journal.pone.0009028

  38. Slatkin DN, Spanne P, Dilmanian FA, Sandborg M (1992) Microbeam radiation therapy. Med Phys 19:1395–1400. https://doi.org/10.1118/1.596771

  39. Slatkin DN, Spanne P, Dilmanian FA, Gebbers JO, Laissue JA (1995) Subacute neuropathological effects of microplanar beams of X-rays from a synchrotron wiggler. Proc Natl Acad Sci 92:8783–8787

  40. Yuan H, Zhang L, Frank JE, Inscoe CR, Burk LM, Hadsell M, Lee YZ, Lu J, Chang S, Zhou O (2015) Treating brain tumor with microbeam radiation generated by a compact carbon-nanotube-based irradiator: initial radiation efficacy study. Radiat Res 184:322–333. https://doi.org/10.1667/rr13919.1

  41. Zhang L, Yuan H, Inscoe C, Chtcheprov P, Hadsell M, Lee Y, Lu J, Chang S, Zhou O (2014) Nanotube X-ray for cancer therapy: a compact microbeam radiation therapy system for brain tumor treatment. Expert Rev Anticancer Ther 14:1411–1418. https://doi.org/10.1586/14737140.2014.978293

  42. Zlobinskaya O, Siebenwirth C, Greubel C, Hable V, Hertenberger R, Humble N, Reinhardt S, Michalski D, Roper B, Multhoff G, Dollinger G, Wilkens JJ, Schmid TE (2014) The effects of ultra-high dose rate proton irradiation on growth delay in the treatment of human tumor xenografts in nude mice. Radiat Res 181:177–183. https://doi.org/10.1667/rr13464.1

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This work has been supported by the Deutsche Forschungsgemeinschaft (MAP C.3.4, CALA) Cluster of Excellence: Munich-Centre for Advanced Photonics as well as the Munich School of BioEngineering of the Technical University of Munich. This work was also supported by the Centre of Advanced Laser Applications with respect to resources necessary for and at the Munich Compact Light Source.

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Correspondence to Thomas E. Schmid.

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The authors declare they have no actual or potential competing financial interests.

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All applicable national and institutional guidelines for the care and use of animals were followed. All procedures performed in this study involving animals were in accordance with ethical standards of the institution at which the study was conducted (project license 55.2-1-54-2531-62-2016).

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Dombrowsky, A.C., Burger, K., Porth, A. et al. A proof of principle experiment for microbeam radiation therapy at the Munich compact light source. Radiat Environ Biophys 59, 111–120 (2020). https://doi.org/10.1007/s00411-019-00816-y

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  • MRT
  • Microbeam
  • Inverse Compton X-ray sources
  • Tumor
  • X-rays
  • Growth delay