A quantitative LC-MS/MS approach for monitoring 2'-fluoro-2'-deoxy-D-glucose uptake in tumor tissue

Purpose: Develop a quantitative LC-MS/MS method for FDG, FDG-monophosphate, glucose and glucose-monophosphate in mouse tumor models to assist in validating the use of [¹⁸F]FDG-positron emission tomography (PET) imaging for anticancer therapies in a clinical setting. Methodology/results: Analytes were isolated from tumors by protein precipitation and detected on a Sciex API-5500 mass spectrometer. Improved assay robustness and selectivity were achieved through chromatographic separation of FDG-monophosphate from glucose-monophosphate, selection of a unique ion transition and incorporation of stable isotope labeled internal standards. In a mouse JIMT-1 tumor model, FDG-monophosphate levels measured by LC-MS/MS correlated with [¹⁸F]FDG-PET imaging results. Conclusion: LC-MS/MS analysis of FDG-monophosphate accumulation in tumors is a cost-effective tool to gauge the translational potential of [¹⁸F]FDG-PET imaging as a noninvasive biomarker in clinical studies.