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

Linnik IV, Scott ML, Holliday KF, Woodhouse N, Waterton JC, O'Connor JP, Barjat H, Liess C, Ulloa J, Young H, Dive C, Hodgkinson CL, Ward T, Roberts D, Mills SJ, Thompson G, Buonaccorsi GA, Cheung S, Jackson A, Naish JH, Parker GJ

Magnetic Resonance in Medicine. 2014;71(5):1854-1862.

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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.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Publication form:
Published date:
Abbreviated journal title:
ISSN:
Volume:
71
Issue:
5
Start page:
1854
End page:
1862
Total:
8
Pagination:
1854-1862
Digital Object Identifier:
10.1002/mrm.24826
Attached files embargo period:
Immediate release
Attached files release date:
24th July, 2014
Access state:
Active

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:229845
Created by:
Holliday, Katherine
Created:
24th July, 2014, 14:41:45
Last modified by:
Holliday, Katherine
Last modified:
8th August, 2014, 19:16:52

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