Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma

Inna V Linnik, Marietta L J Scott, Katherine F Holliday, Neil Woodhouse, John C Waterton, James P B O'Connor, Hervé Barjat, Carsten Liess, Jose Ulloa, Helen Young, Caroline Dive, Cassandra L Hodgkinson, Tim Ward, Darren Roberts, Samantha J Mills, Gerard Thompson, Giovanni A Buonaccorsi, Susan Cheung, Alan Jackson, Josephine H NaishGeoff J M Parker

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: There is a clinical need for noninvasive, nonionizing imaging biomarkers of tumor hypoxia and oxygenation. We evaluated the relationship of T1 -weighted oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements to histopathology measurements of tumor hypoxia in a murine glioma xenograft and demonstrated technique translation in human glioblastoma multiforme.

METHODS: Preclinical evaluation was performed in a subcutaneous murine human glioma xenograft (U87MG). Animals underwent OE-MRI followed by dynamic contrast-enhanced MRI (DCE-MRI) and histological measurement including reduced pimonidazole adducts and CD31 staining. Area under the curve (AUC) was measured for the R1 curve for OE-MRI and the gadolinium concentration curve for DCE-MRI. Clinical evaluation in five patients used analogous imaging protocols and analyses.

RESULTS: Changes in AUC of OE-MRI (AUCOE ) signal were regionally heterogeneous across all U87MG tumors. Tumor regions with negative AUCOE typically had low DCE-MRI perfusion, had positive correlation with hypoxic area (P = 0.029), and had negative correlation with vessel density (P = 0.004). DCE-MRI measurements did not relate to either hypoxia or vessel density in U87MG tumors. Clinical data confirmed comparable signal changes in patients with glioblastoma.

CONCLUSION: These data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.

Original languageEnglish
Pages (from-to)1854-1862
Number of pages9
JournalMagnetic Resonance in Medicine
Volume71
Issue number5
Early online date24 Jun 2013
DOIs
Publication statusPublished - May 2014

Keywords

  • Animals
  • Biomarkers, Tumor
  • Brain Neoplasms
  • Cell Hypoxia
  • Cell Line, Tumor
  • Female
  • Glioblastoma
  • Glioma
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Oximetry
  • Oxygen
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution

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