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Development of a novel animal model to differentiate radiation necrosis from tumor recurrence

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An Erratum to this article was published on 24 April 2012

Abstract

Distinguishing tumor progression from radiation necrosis after treatment in patients with brain tumors presents a clinical dilemma. A well-characterized, orthotopic rodent model of radiation-induced brain necrosis including a tumor is not currently available The objective of the study was to create focal radiation necrosis in rat brain bearing human glioblastoma (GBM) using stereotactic radiosurgery and confirm it by immuno-histological analysis. Nude rats implanted with primary GBM cells were irradiated using a stereotactic setup (n = 3) or received no radiation (n = 3). Ten weeks after the implantation, growth of the tumor was confirmed by magnetic resonance imaging (MRI). For each animal, MRI and contrast-enhanced CT images were obtained and fused using registration software. The tumor was identified and delineated using the fused CT/MR images. A treatment plan was generated using a 4 mm radiosurgery cone such that one portion of the tumor receives 100% dose of 60 Gy sufficient to cause necrosis, whereas the tumor edge at depth receives only 50% or less dose, allowing for regrowth of the tumor. The brains were collected 10 weeks after irradiation and immuno-histological analysis was performed. Hematoxylin and eosin staining showed central liquefaction necrosis in the high dose region consistent with necrosis and viable tumor in the peripheral low dose region. Ki-67 staining showed highly proliferative tumor cells surrounding the necrotic parts of the tumor. Luxol fast blue and lectin staining showed demyelination and vascular injury in brain tissue consistent with radiation necrosis. We have developed a novel model of radiation necrosis in rats bearing glioma.

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Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, 48202, USA

    Sanath Kumar, Jinkoo Kim & Stephen L. Brown

  2. Department of Radiology, Henry Ford Health System, Detroit, MI, 48202, USA

    Ali S. Arbab, Rajan Jain & Adarsh Shankar

  3. Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, 48202, USA

    Ana C. deCarvalho & Tom Mikkelsen

Authors
  1. Sanath Kumar
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  2. Ali S. Arbab
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  3. Rajan Jain
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  4. Jinkoo Kim
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  5. Ana C. deCarvalho
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  6. Adarsh Shankar
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  7. Tom Mikkelsen
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  8. Stephen L. Brown
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Correspondence to Sanath Kumar.

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Kumar, S., Arbab, A.S., Jain, R. et al. Development of a novel animal model to differentiate radiation necrosis from tumor recurrence. J Neurooncol 108, 411–420 (2012). https://doi.org/10.1007/s11060-012-0846-z

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  • DOI: https://doi.org/10.1007/s11060-012-0846-z

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