Metabolic fate of 18F-FDG in mice bearing either SCCVII squamous cell carcinoma or C3H mammary carcinoma.

Abstract

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. 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). 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. 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.