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Basic and Translational Investigations |
1 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Brain Tumor Research Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
2 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
3 Brain Tumor Research Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: bbedell{at}bic.mni.mcgill.ca.
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Abstract |
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The increasing development of novel anticancer agents demands parallel advances in the methods used to rapidly assess their therapeutic efficacy (TE) in the preclinical phase. We evaluated the ability of small-animal PET, using the 18F-fluoro-deoxy-D-glucose (FDG) radiotracer, to predict the TE of a number of anticancer agents in the rat C6 glioma model following 3 days of treatment. Semiquantitative measurements of changes in FDG uptake during the course of treatment (standardized uptake value response [SUVr]) were found to be significantly lower in tumors treated with the hypoxia-inducible factor-1a inhibitor YC-1 (15 mg/kg) than in tumors in the control group. No significant SUVr change was observed following a similar 3-day regimen with the proapoptotic agent NS1619 (20 mg/kg), the combination of YC-1 and NS1619, or the alkylating agent temozolomide (7.5 mg/kg). Quantitative immunohistochemical studies demonstrated significantly lower levels of glucose transporter-1 (GLUT-1) expression in the YC-1-treated tumors, thereby correlating with the low SUVr observed in this group. The ability of SUVr to predict gold-standard outcomes of TE was further validated as YC-1-treated tumors had decreased volumes compared to control tumors. As such, we successfully demonstrated the ability of FDG-PET to rapidly determine the TE of novel agents for the treatment of glioma in the preclinical phase of evaluation.
Key Words: anticancer agents, C6 glioma, 18F-fluoro-deoxy-D-glucose, positron emission tomography, therapeutic efficacy
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