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FDG-PET imaging for the evaluation of antiglioma agents in a rat model

McConnell Brain Imaging Centre (S.A., A.A., A.C.E., B.J.B.) and Brain Tumor Research Centre (S.A., R.F.D.M.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

Address all correspondence to Barry J. Bedell, McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University St., Montreal, QC, Canada H3A 2B4 (bbedell{at}bic.mni.mcgill.ca).

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. Semi-quantitative measurements of changes in FDG uptake during the course of treatment (standardized uptake value response [SUV_r]) were found to be significantly lower in tumors treated with the hypoxia-inducible factor-1 inhibitor YC-1 (15 mg/kg) than in tumors in the control group. No significant SUV_r change was observed following a similar 3-day regimen with the proapoptotic agent NS1619 (20 µg/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 SUV_r observed in this group. The ability of SUV_r 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-fluorodeoxy-D-glucose • positron emission tomography • therapeutic efficacy

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