Ketogenic diet as a tool for enhancing 2-[18 F]FDG accumulation in lung adenocarcinoma with lepidic-predominant growth

Purpose: The aim of the present study is to assess if 2-[¹⁸F]FDG uptake can be enhanced by subjecting human ADK-LPA derived cell lines and murine models carrying ADK-LPA to a low-glucose intake dietary regimen so to potentially ameliorate the CT/PET sensitivity in human patients. Methods: A dietary regimen envisaging a low glucose uptake (ketogenic diet) and a normal diet were applied to a human ADK-LPA derived cell line (NCI-H358) and to other two lung carcinoma cell lines (A549 and NCI-H1299) for comparison purposes. Cells were afterwards incubated with 2-[¹⁸F]FDG. Moreover, the correspondent regimens were enforced on murine models carrying ADK-LPA xenografts to evaluate the influence of the diet on the 2-[¹⁸F]FDG biodistribution and visualization upon injection. Results: As expected, when incubated with glucose-rich medium, NCI-H358 (ADK-LPA) cells have a really low [¹⁸F]FDG uptake (up to 4-fold less) compared to A549 and NCI- H1299 cells. On the other hand, when a glucose-depleted medium is used, a significantly enhanced uptake in NCI-H358 cells respect to the other two lines (up to 10-fold higher after 5 days) was obtained. In the PET/CT images, tumors are clearly better visualized in mice subjected to ketogenic diet respect to control group already after 3 days. Conclusion: The study attested how 2-[¹⁸F]FDG uptake in a low glucose dependent tumor, usually not detected by PET/CT, can be controlled in vitro and in murine models by a dietary regimen. The outputs of this study open the way to a possible method to improve the [¹⁸F]FDG-PET/CT performances in the detection of ADK-LPA thus laying the foundations of a possible future application in humans.