Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic Resonance, and Positron Emission Tomography Imaging

Methods Mol Biol. 2018:1742:301-320. doi: 10.1007/978-1-4939-7665-2_26.

Abstract

Gliomas are the most common type of primary, malignant brain tumor and significantly impact patients, who have a median survival of ~1 year depending on mutational background. Novel imaging modalities such as luciferase bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized tomography (micro-CT), and micro-positron emission tomography (micro-PET) have expanded the portfolio of tools available to study this disease. Hypoxia, a key oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by the concomitant use of noninvasive MRI and PET imaging. We present a protocol involving stereotactic injection of syngenic F98 luciferase-expressing glioma cells generated by our laboratory into Fischer 344 rat brains and imaging using luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F-fluorothymidine PET imaging are compared with quantified luciferase flux. These tools can potentially be used for assessing tumor growth characteristics, hypoxia, mutational effects, and treatment effects.

Keywords: 18F–fluoromisonidazole; 18F–fluorothymidine; Animal magnetic resonance imaging; Bioluminescence; Glioma; Luciferase.

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Fluorodeoxyglucose F18 / metabolism
  • Glioma / diagnostic imaging*
  • Glioma / metabolism
  • Humans
  • Luciferases / metabolism*
  • Luminescent Proteins / metabolism
  • Magnetic Resonance Imaging / veterinary
  • Multimodal Imaging / methods*
  • Multimodal Imaging / veterinary
  • Positron-Emission Tomography / veterinary
  • Radiopharmaceuticals / metabolism
  • Rats

Substances

  • Luminescent Proteins
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Luciferases