In a second application, [18F]Me-4FDG was used to identify early-stage lung adenocarcinoma (LADC) using PET. [18F]FDG struggles to identify early invasive disease because of relatively low GLUT expression and glucose utilization. This is consistent with increased GLUT expression correlating to tumor progression towards poorly differentiated “high-grade” LADC. In contrast, cells in early stage “low-grade” lesions primarily use SGLT2 for glucose transport. With this in mind, [18F]Me-4FDG was able to detect lung tumors at an earlier stage than [18F]FDG in genetically engineered mouse models, with sustained uptake along disease progression. Check this out and their work with patient-derived xenografts at
Science Translational Medicine (DOI:
10.1126/scitranslmed.aat5933).
In addition to the potential for earlier and more sensitive detection of tumors, [18F]Me-4FDG also points to many new potential lines of inquiry. For example, recently several SGLT2 inhibitors have reached the market as treatments for type II diabetes mellitus. Based on the above results, this class of drugs (gliflozins) may also hold potential for treatment of certain types of cancer at a stage when they are dependent on this “alternative” glucose transporter. Indeed, the Science Translational Medicine paper discussed above contains a preclinical trial towards that end.
For myself, the [18F]Me-4FDG story so far is a nice reminder that in molecular imaging it is not just the functional outcomes but also the mechanisms that matter.
Benjamin Rotstein is an Assistant Professor at University of Ottawa and Scientist at University of Ottawa Heart Institute. His lab conducts research into synthetic radiochemical methods with PET isotopes as well as radiotracer development, with an emphasis on cardiovascular applications. Follow their progress at rotsteinlab.com