Incongruity of imaging using fluorescent 2-DG conjugates compared to ¹⁸F-FDG in preclinical cancer models

Purpose: We compared the use of near-infrared conjugates of 2-deoxyglucose (NIR 2-DG) to 2-deoxy-2-[¹⁸ F]fluoro-D-glucose (¹⁸ F-FDG) for the purposes of imaging tumors, as well as response to therapy. Procedures: Uptake of both ¹⁸ F-FDG and NIR 2-DG within gastrointestinal stromal tumor xenografts were imaged before and after nilotinib treatment. Confocal microscopy was performed to determine NIR 2-DG distribution in tumors. Results: Treatment with nilotinib resulted in a rapid reduction in ¹⁸ F-FDG uptake and reduced tumor cell viability which was predictive of long-term antitumor efficacy. In contrast, optical imaging with NIR 2-DG probes was unable to differentiate control from niltonib-treated animals, and microscopic analysis revealed no change in probe distribution as a result of treatment. Conclusions: These results suggest that conjugation of large bulky fluorophores to 2-DG disrupts the facilitated transport and retention of these probes in cells. Therefore, optical imaging of NIR 2-DG probes cannot substitute for ¹⁸ F-FDG positron emission tomography imaging as a biomarker of tumor cell viability and metabolism.