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

Sanath Kumar, Ali Syed Arbab, Rajan Jain, Jinkoo Kim, Ana C. DeCarvalho, Adarsh Shankar, Tom Mikkelsen, Stephen L. Brown

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalJournal of Neuro-Oncology
Volume108
Issue number3
DOIs
StatePublished - Jul 2012

Keywords

  • Glioma
  • Radiation necrosis
  • Radiosurgery
  • Recurrence

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Development of a novel animal model to differentiate radiation necrosis from tumor recurrence'. Together they form a unique fingerprint.

  • Cite this

    Kumar, S., Arbab, A. S., Jain, R., Kim, J., DeCarvalho, A. C., Shankar, A., Mikkelsen, T., & Brown, S. L. (2012). Development of a novel animal model to differentiate radiation necrosis from tumor recurrence. Journal of Neuro-Oncology, 108(3), 411-420. https://doi.org/10.1007/s11060-012-0846-z