Abstract

Extracellular acidosis and significant amino acid uptake are hallmarks of gliomas. Chemical exchange saturation transfer (CEST) MRI targeted the amine protons on amino acids can serve as a combined amino acid and pH-weighted biomarker with a high specificity for active tumor. We hypothesized that amine CET MRI may provide similar specificity, but higher spatial resolution, compared with 18F-FDOPA PET and that regions of increased amine CEST contrast may contain regions of active proliferating tumor. Eighteen glioma patients underwent pH-weighted amine CEST MRI prior to surgical resection and biopsy. Of these, eight also had 18F-FDOPA PET data acquired prior to surgery. PET and CEST data were registered to anatomical images. ROIs were defined on the highest 20% and lowest 20% of PET uptake values within the FLAIR-enhancing region and the CEST contrast within these ROIs was calculated. Among the larger cohort of eighteen patients, an acidic and non-acidic target was defined by CEST MRI and biopsied during surgery. These samples were stained for Ki67 and HIF1a. Amine CEST MRI and 18F-FDOPA PET uptake showed similar patterns of abnormality and regions of elevated CEST contrast also showed significantly elevated 18F-FDOPA uptake (P=0.002). Elevated CEST contrast showed significantly higher expression of Ki67 compared to non-acidic targets (P=0.034). HIF1a expression was correlated with CEST contrast. Amine CEST MRI provides contrast dependent on both amino acid concentration and pH, provides similar specificity and higher spatial resolution when compared with 18F-FDOPA PET, and is significantly correlated with histological measures of active, hypoxic tumor.

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