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11.07.2016 | Original Article

Novel technique for high-precision stereotactic irradiation of mouse brains

verfasst von: J. Hartmann, J. Wölfelschneider, C. Stache, R. Buslei, A. Derer, M. Schwarz, T. Bäuerle, R. Fietkau, U. S. Gaipl, C. Bert, A. Hölsken, B. Frey

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 11/2016

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Abstract

Background and purpose

Small animal irradiation systems were developed for preclinical evaluation of tumor therapy closely resembling the clinical situation. Mostly only clinical LINACs are available, so protocols for small animal partial body irradiation using a conventional clinical system are essential. This study defines a protocol for conformal brain tumor irradiations in mice.

Materials and methods

CT and MRI images were used to demarcate the target volume and organs at risk. Three 6 MV photon beams were planned for a total dose of 10 fractions of 1.8 Gy. The mouse position in a dedicated applicator was verified by an X‑ray patient positioning system before each irradiation. Dosimetric verifications (using ionization chambers and films) were performed. Irradiation-induced DNA damage was analyzed to verify the treatment effects on the cellular level.

Results

The defined treatment protocol and the applied fractionation scheme were feasible. The in-house developed applicator was suitable for individual positioning at submillimeter accuracy of anesthetized mice during irradiation, altogether performed in less than 10 min. All mice tolerated the treatment well. Measured dose values perfectly matched the nominal values from treatment planning. Cellular response was restricted to the target volume.

Conclusion

Clinical LINAC-based irradiations of mice offer the potential to treat orthotopic tumors conformably. Especially with respect to lateral penumbra, dedicated small animal irradiation systems exceed the clinical LINAC solution.

Tillner F, Thute P, Buetof R, Krause M, Enghardt W (2014) Pre-clinical research in small animals using radiotherapy technology – a bidirectional translational approach. Z Med Phys 24(4):335–351. doi:10.1016/j.zemedi.2014.07.004 CrossRefPubMed

Kuess P, Bozsaky E, Hopfgartner J, Seifritzl G, Doerr W, Georg D (2014) Dosimetric challenges of small animal irradiation with a commercial X‑ray unit. Z Med Phys 24(4):363–372. doi:10.1016/j.zemedi.2014.08.005 CrossRefPubMed

Frenzel T, Grohmann C, Schumacher U, Kruell A (2014) Partial body irradiation of small laboratory animals with an industrial X‑ray tube. Z Med Phys 24(4):352–362. doi:10.1016/j.zemedi.2014.02.002 CrossRefPubMed

Derer A, Frey B, Fietkau R, Gaipl US (2015) Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother. doi:10.1007/s00262-015-1771-8 PubMed

De Ryck T, Van Impe A, Vanhoecke BW, Heyerick A, Vakaet L, De Neve W, Muller D, Schmidt M, Dorr W, Bracke ME (2015) 8‑prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis : cell culture and murine model. Strahlenther Onkol 191(5):429–436. doi:10.1007/s00066-014-0782-2 CrossRefPubMed

Muth C, Rubner Y, Semrau S, Ruhle PF, Frey B, Strnad A, Buslei R, Fietkau R, Gaipl US (2015) Primary glioblastoma multiforme tumors and recurrence: comparative analysis of the danger signals HMGB1, HSP70, and calreticulin. Strahlenther Onkol. doi:10.1007/s00066-015-0926-z PubMed

Clarkson R, Lindsay PE, Ansell S, Wilson G, Jelveh S, Hill RP, Jaffray DA (2011) Characterization of image quality and image-guidance performance of a preclinical microirradiator. Med Phys 38(2):845–856CrossRefPubMedPubMedCentral

Wong J, Armour E, Kazanzides P, Iordachita U, Tryggestad E, Deng H, Matinfar M, Kennedy C, Liu ZJ, Chan T, Gray O, Verhaegen F, McNutt T, Ford E, DeWeese TL (2008) High-resolution, small animal radiation research platform with X‑ray tomographic guidance capabilities. Int J Radiat Oncol Biol Phys 71(5):1591–1599. doi:10.1016/j.ijrobp.2008.04.025 CrossRefPubMedPubMedCentral

Tillner F, Hietschold V, Khaless A, Pawelke J, Thute P, Enghardt W (2010) Characterization and optimization of the imaging and dosimetric properties of a image-guided precision irradiation device for small animals. Strahlenther Onkol 186:105–105

10.

Yoshizumi T, Brady SL, Robbins ME, Bourland JD (2011) Specific issues in small animal dosimetry and irradiator calibration. Int J Radiat Biol 87(10):1001–1010. doi:10.3109/09553002.2011.556178 CrossRefPubMedPubMedCentral

11.

Felix MC, Fleckenstein J, Kirschner S, Hartmann L, Wenz F, Brockmann MA, Glatting G, Giordano FA (2015) Image-guided radiotherapy using a modified industrial Micro-CT for preclinical applications. PLoS ONE 10(5):11. doi:10.1371/journal.pone.0126246 CrossRef

12.

Wang W‑C, Liang S‑L, Chen Y‑K, Lin L‑M (2008) The therapeutic effect of fractionated radiation on DMBA-induced hamster buccal pouch squamous cell carcinomas. Oral Oncol 44:1160–1166. doi:10.1016/j.oraloncology.2008.03.001 CrossRefPubMed

13.

Song KH, Pidikiti R, Stojadinovic S, Speiser M, Seliounine S, Saha D, Solberg TD (2010) An x‑ray image guidance system for small animal stereotactic irradiation. Phys Med Biol 55(23):7345–7362. doi:10.1088/0031-9155/55/23/011 CrossRefPubMed

14.

Rodriguez M, Zhou H, Keall P, Graves E (2009) Commissioning of a novel microCT/RT system for small animal conformal radiotherapy. Phys Med Biol 54(12):3727–3740. doi:10.1088/0031-9155/54/12/008 CrossRefPubMedPubMedCentral

15.

Verhaegen F, van Hoof S, Granton PV, Trani D (2014) A review of treatment planning for precision image-guided photon beam pre-clinical animal radiation studies. Z Med Phys 24(4):323–334. doi:10.1016/j.zemedi.2014.02.004 CrossRefPubMed

16.

Verhaegen F, Granton P, Tryggestad E (2011) Small animal radiotherapy research platforms. Phys Med Biol 56(12):R55–R83. doi:10.1088/0031-9155/56/12/r01 CrossRefPubMed

17.

Stache C, Holsken A, Schlaffer SM, Hess A, Metzler M, Frey B, Fahlbusch R, Flitsch J, Buchfelder M, Buslei R (2015) Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model. Brain Pathol 25(1):1–10. doi:10.1111/bpa.12148 CrossRefPubMed

18.

Jin JY, Yin FF, Tenn SE, Medin PM, Solberg TD (2008) Use of the BrainLAB ExacTrac X‑Ray 6D system in image-guided radiotherapy. Med Dosim 33(2):124–134. doi:10.1016/j.meddos.2008.02.005 CrossRefPubMed

19.

Mah LJ, El-Osta A, Karagiannis TC (2010) gammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 24(4):679–686. doi:10.1038/leu.2010.6 CrossRefPubMed

20.

Stache C, Holsken A, Fahlbusch R, Flitsch J, Schlaffer SM, Buchfelder M, Buslei R (2014) Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth. Neuro-oncology 16(2):256–264. doi:10.1093/neuonc/not195 CrossRefPubMed

21.

Low DA, Mutic S, Dempsey JF, Gerber RL, Bosch WR, Perez CA, Purdy JA (1998) Quantitative dosimetric verification of an IMRT planning and delivery system. Radiother Oncol 49(3):305–316CrossRefPubMed

22.

Gutmann DH, Hunter-Schaedle K, Shannon KM (2006) Harnessing preclinical mouse models to inform human clinical cancer trials. J Clin Invest 116(4):847–852. doi:10.1172/jci28271 CrossRefPubMedPubMedCentral

23.

Lee S‑H, Kim J‑Y, Lee K‑C, Nam J‑S, Choi J, Lee S‑H, Sung K‑H, Ahn S‑H (2014) Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model. Lab Anim Res 30:64–72. doi:10.5625/lar.2014.30.2.64 CrossRefPubMedPubMedCentral

24.

Bert C, Richter D, Durante M, Rietzel E (2012) Scanned carbon beam irradiation of moving films: comparison of measured and calculated response. Radiat Oncol 7:55. doi:10.1186/1748-717x-7-55 CrossRefPubMedPubMedCentral

25.

Bache ST, Juang T, Belley MD, Koontz BF, Adamovics J, Yoshizumi TT, Kirsch DG, Oldham M (2015) Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters. Med Phys 42(2):846–855. doi:10.1118/1.4905489 CrossRefPubMedPubMedCentral

26.

Welch D, Harken AD, Randers-Pehrson G, Brenner DJ (2015) Construction of mouse phantoms from segmented CT scan data for radiation dosimetry studies. Phys Med Biol 60:3589–3598CrossRefPubMedPubMedCentral

Titel: Novel technique for high-precision stereotactic irradiation of mouse brains
verfasst von: J. Hartmann
J. Wölfelschneider
C. Stache
R. Buslei
A. Derer
M. Schwarz
T. Bäuerle
R. Fietkau
U. S. Gaipl
C. Bert
A. Hölsken
B. Frey
Publikationsdatum: 11.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 11/2016
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-016-1014-8

Springer Medizin

Novel technique for high-precision stereotactic irradiation of mouse brains