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Metabolic Fate of ¹⁸F-FDG in Mice Bearing Either SCCVII Squamous Cell Carcinoma or C3H Mammary Carcinoma

¹ PET Center, Aarhus University Hospital, Aarhus, Denmark
² Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
³ Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark

Tumors often have an increased uptake of glucose and can be detected by PET imaging using ¹⁸F-FDG. ¹⁸F-FDG is converted to ¹⁸F-FDG-6-phosphate (¹⁸F-FDG-6-P), and the usual assumption is that ¹⁸F-FDG-6-P is not a substrate for subsequent enzymatic reactions and that tumor hot spots reflect trapping of ¹⁸F-FDG-6-P. We recently found, however, that in the pig liver, ¹⁸F-FDG is metabolized not only to ¹⁸F-FDG-6-P but also to the subsequent oxygenation product 2-¹⁸F-fluoro-2-deoxy-6-phospho-D-glucononate (¹⁸F-FD-PG1). We therefore wished to characterize the metabolism of ¹⁸F-FDG in experimental tumors in mice. Methods: ¹⁸F-FDG was given intravenously to mice with either SCCVII squamous cell carcinoma or C3H mammary carcinoma grown on the back. ¹⁸F-Labeled metabolites were determined by radio-high-performance liquid chromatography in tumor tissue biopsies, in a time course of 180 min (12 mice of each tumor type), and in liver tissue biopsies 80 min after tracer injection (2 mice of each type). Results: After the tracer injection, not only ¹⁸F-FDG and ¹⁸F-FDG-6-P but also ¹⁸F-FD-PG1 and 2-¹⁸F-fluoro-2-deoxy-1,6-biphosphate were detected in both tumors, relatively more in SCCVII carcinoma than in C3H carcinoma. Both tumors accumulated radioactivity throughout the 180-min measurement period, 4-fold more in SCCVII carcinoma than in C3H carcinoma. At 80 min, the radioactivity was approximately 6 and 1.2 times higher in the respective tumors than in liver tissue. Conclusion: Our results agree with the general finding that most malignant tumor tissues accumulate significantly more ¹⁸F-radioactivity than do normal tissues, but our results do not support the concept that this increase is caused solely by accumulation of ¹⁸F-FDG-6-P. Furthermore, the rate of ¹⁸F-FDG metabolism was higher in SCCVII carcinoma than in C3H carcinoma.

Key Words: tumor glucose metabolism • ¹⁸F-FDG PET • SCCVII squamous cell carcinoma • C3H mammary carcinoma

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