In vivo Fluorine Metabolic Imaging (FMI) with 3-Fluorodeoxy-Sugars: A Paradigm Shift in Metabolic Imaging

Motivation: To develop a molecular MRI approach for non-invasive mapping of unexplored metabolic pathways of sugars, beyond the well-studied glycolysis. Goal(s): We introduce Fluorine Metabolic Imaging (FMI), utilizing 3-fluorodeoxy-glucose (3FDG) and 3-fluorodeoxy-galactose (3FDGal), to concurrently map the spatial distribution of sugar-oxidizing and -reducing (but not -phosphorylating) enzymes. Approach: Phantom and in vivo FMI in mice. Results: 19F-MRI experiments demonstrated the ability to spectrally differentiate and spatially map the probes and downstream metabolites, highlighting the superiority of 3FDGal. Shifting the spotlight of metabolic imaging towards FMI with 3FDGal opens up new frontiers in imaging, potentially revealing hidden aspects of sugar metabolism in health and disease. Impact: FMI with 3FDGal constitutes a robust platform with high metabolite yield, offering an MRI-based approach to studying sugar reduction versus oxidation for the first time. The outlined FMI principles could be extended for imaging additional pathways with other 19F-labeled compounds.