Accumulation of 2-deoxy-2-[18F]fluoro-D-galactose in the liver by phosphate and uridylate trapping.

To investigate the highest accumulation of 2-deoxy-2-[18F]fluoro-D-galactose ([18F]FdGal) in the liver, metabolic studies with [18F]FdGal were carried out in Wistar rats for 120 min after i.v. injection. As main metabolites 2-deoxy-2-[18F]fluoro-D-galactose 1-phosphate ([18F]FdGal-1-P) and UDP-2-deoxy-2-[18F]-fluoro-D-galactose (UDP-[18F]FdGal) were identified in the liver and other tissues. The [18F]FdGal was phosphorylated by galactokinase. The phosphorylation rate was very rapid in the liver, in which at 5 min after injection 81% of 18F was detected as [18F]FdGal-1-P. After this time the phosphate form decreased with time, which was explained by conversion of [18F]FdGal-1-P to UDP-[18F]FdGal by UDP-glucose: galactose-1-phosphate uridyltransferase. At 120 min after injection 77% of the 18F was measured in the UDP-[18F]FdGal. In the brain both reaction rates were slower than in the liver. Both phosphate and uridylate derivates were also observed as main metabolites in the heart, lung, spleen and small intestine. On the other hand, a small amount of [18F]FdGal-1-P was detected in the plasma, in which the percentage of phosphate increased gradually and was 6% at 120 min. These results show that the [18F]FdGal metabolism in tissue results in phosphate and uridylate trapping and that the [18F]FdGal has potential for measuring in vivo galactose metabolism with positron emission tomography.