Objective: To investigate the impact of different tracer modifications on the imaging of cancer metabolism, focusing on the comparison of fluorescent glucose-analog tracers (2-NBDG and 2-DG-750) and the radiolabeled tracer 18F-FDG in both in-vitro and in-vivo settings.

Methods: We conducted an in-vitro comparative study using four cancer cell lines, each with unique glucose uptake characteristics. The study involved direct comparison of three tracers: 2-NBDG, 2-DG-750 and 18F-FDG, examining their internalization behaviors, metabolic functionality and localization effects in cancer metabolism imaging.

Results: The study revealed that each tracer exhibits distinct internalization behaviors correlated with imaging label size and type. 18F-FDG showed the highest uptake efficiency. Fluorescent molecules were found to accumulate in tumors primarily due to hydrophobic interactions and possible aggregation, indicating inefficiency in metabolism and suitability for imaging metabolic phenomena when compared to radiolabeled biomolecules.

Conclusion: Our findings demonstrate that despite certain impracticalities, nuclear imaging, particularly using radiolabeled biomolecules like 18F-FDG, offers significant potential for accurately capturing biological phenomena. This is crucial for future advancements in both clinical and research settings. The study emphasizes the limitations of fluorescent molecules in imaging metabolic activities due to their inefficient metabolism and aggregation tendencies.

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