Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo?

The significance of L-[methyl-11C]methionine (11C-Met), L-[1-11C]leucine (11C-Leu) and L-2-[18F]fluorotyrosine (18F-Tyr) for measuring protein synthesis rates in the brain and in tumors by PET was re-evaluated. Tissue uptake and protein incorporation of 3H-Met, 14C-Leu and 18F-Tyr were investigated in mice bearing the FM3A mammary carcinoma. In the control group, the uptake of all three tracers in the brain and FM3A and their incorporation into the acid-precipitable fraction (APF) increased over 60 min. When the protein synthesis in vivo was inhibited by cycloheximide, the incorporation of all three tracers into the APF was significantly reduced to 6%-32% and 3%-11% of the control in the brain and FM3A, respectively. Under these conditions, total uptake of 14C-Leu in the brain and FM3A decreased rapidly, and most of the 14C in the APF was detected as proteins. On the other hand, 3H-Met and 18F-Tyr uptake continued to increase, and significant amounts of radioactivity were incorporated into nonprotein materials. In mice given ouabain to inhibit amino acid transport, total uptake of all three amino acids by FM3A was reduced to 67%-74% of the control 5 min postinjection. These results demonstrate that uptake of the three amino acids is affected by alterations in the amino acid transport system in the brain and tumor tissues, but that only 14C-Leu uptake reflects protein synthesis rates.