Metabolites of (18)F-FDG and 3-O-(11)C-methylglucose in pig liver

PET uses (18)F-FDG widely to estimate glucose metabolism in vivo. Dynamic PET data are evaluated by kinetic models of the metabolic pathways. Knowledge of the metabolites of FDG is of critical importance for the interpretation of kinetic PET studies. The purpose of this study was to determine the metabolic pathways of FDG and 3-O-(11)C-methylglucose (MG) in liver tissue in vivo. It is usually assumed that MG is not metabolized and FDG is converted to (18)F-FDG-6-phosphate (FDG-6-P).

The study was performed on 6 anesthetized 40-kg pigs that were given the 2 tracers intravenously. The content of metabolites was determined in successive liver tissue biopsies. Freeze-clamped liver tissue samples were subjected to extraction by acetonitrile at -5 degrees C to -10 degrees C, and extracts were analyzed by radio-high-performance liquid chromatography (radio-HPLC). The findings were identified by means of radio-HLPC measurements of the products of in vitro enzymatic reactions.

The applied extraction technique provided almost quantitative recovery of the radioactivity from tissue. After MG injection, only MG was detectable in the liver tissue; no labeled metabolites were found. After FDG injection, 2 metabolites were identified, FDG-6-P and 2-(18)F-fluoro-2-deoxy-6-phosphogluconate (FD-6-PG1). The tissue content of FDG increased rapidly, and, after 5 min, only FDG was identified; hereafter, the fraction of FDG decreased to approximately 40% of the tissue radioactivity after 180 min. After 20 min, FDG-6-P was found in each of the pigs and it increased throughout the measurement period of 180 min, with a somewhat slower rise at late time points. FD-6-PG1 began to appear in the liver tissue after 45 min and increased throughout the 180-min experiment, with the increase somewhat slower than that of FDG-6-P. After 180 min, approximately 40% of the metabolites was attributed to FD-6-PG1. The content of other metabolites was <2%, even after 180 min.

After the FDG injection, not only FDG-6-P but also FD-6-PG1 were formed in the liver. Any possible incorporation of FDG into glycogen was of minor importance.