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MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the Small Animal Radiation Research Platform (SARRP)

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Abstract

Current glioblastoma (GB) small animal models for cranial radiation therapy (RT) use simple single beam technologies, which differ from the advanced conformal image-guided radiation techniques used in clinical practice. This technological disparity presents a major disadvantage for the development of new therapeutic approaches. Hence, we established a F98 GB rat model using magnetic resonance imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small Animal Radiation Research Platform (SARRP). Ten Fischer rats were inoculated with F98 tumor cells. When the tumor reached a volume of approximately 27 mm3 on T2-weighted MR images, the animals were randomized into a treatment group (n = 5) receiving RT and concomitant temozolomide, and a sham group (n = 5) receiving control injections. For the treated animals, contrast-enhanced T1-weighted MR images were acquired followed by a cone-beam computed tomography (CBCT) on the SARRP system. Both scans were co-registered; MRI was used to define the target whereas CBCT was used for calculating a dose plan (20 Gy, three non-coplanar arc beams, 3 × 3 mm collimator). Tumor volumes were evaluated on follow-up contrast-enhanced T1-weighted MR images. Verification of treatment accuracy with γH2AX immunohistochemical staining was performed. Tumors in the control animals showed rapid proliferation during follow-up, encompassing almost the entire right cerebral hemisphere at day 12–15. Treated animals showed no significant tumor growth from 2 to 9 days post RT. γH2AX results confirmed the accuracy of dose delivery. This model, which is quite similar to the approach in the clinic, is valid for combined RT and chemotherapy of GB in rats.

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Acknowledgments

We would like to thank Stichting Luka Hemelaere who supported this work. The SARRP system was funded by Stichting tegen kanker. Christian Vanhove is supported by the GROUP-ID consortium.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Julie Bolcaen & Ingeborg Goethals

  2. Department of Electronics and Information Systems, iMinds-IBiTech-MEDISIP, Ghent University, Ghent, Belgium

    Benedicte Descamps & Christian Vanhove

  3. Department of Radiology, Ghent University Hospital, Ghent, Belgium

    Karel Deblaere

  4. Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium

    Tom Boterberg

  5. Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium

    Giorgio Hallaert

  6. Department of Pathology, Ghent University Hospital, Ghent, Belgium

    Caroline Van den Broecke

  7. Department of Basic Medical Sciences—Physiology Group, Ghent University, Ghent, Belgium

    Elke Decrock & Luc Leybaert

  8. Department of Basic Medical Sciences—Histology Group, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium

    Anne Vral

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  1. Julie Bolcaen
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  2. Benedicte Descamps
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  8. Anne Vral
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  9. Luc Leybaert
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  10. Christian Vanhove
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  11. Ingeborg Goethals
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Correspondence to Ingeborg Goethals.

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Bolcaen, J., Descamps, B., Deblaere, K. et al. MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the Small Animal Radiation Research Platform (SARRP). J Neurooncol 120, 257–266 (2014). https://doi.org/10.1007/s11060-014-1552-9

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  • DOI: https://doi.org/10.1007/s11060-014-1552-9

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