A quantitative LC–MS/MS Approach for Monitoring 2′-Fluoro-2′-Deoxy-D-Glucose Uptake in Tumor Tissue

Abstract

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.

Keywords::

• FDG-PET
• FDG
• fluorodeoxyglucose
• LC–MS/MS assay
• mass spectrometry
• tumor

Acknowledgments

The authors thanked B Albuquerque (CVMED Research, Pfizer Inc., MA, USA) for providing the nontumor tissue samples for this manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.