Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography.

The principles and initial results of the use of PET to measure the local cerebral metabolic rate for protein synthesis ( lCRPS ) in humans are described. The labeling of leucine, phenylalanine, and methionine in the carboxyl position provides a strategy (selective position labeling) for discriminating between the incorporation of these amino acids into proteins and metabolic oxidation. In metabolic oxidation the label is removed from tissue through decarboxylation. The resulting labeled carbon dioxide is diluted by the tissue carbon dioxide pool, cleared from cerebral tissue by blood flow, and subsequently ventilated by the lungs. This approach also provides a plasma input function that is free of other labeled amino acids produced through systemic reactions, such as those that occur for methionine labeled in the methyl group. The measured lCRPS is in good agreement with values determined by Smith and Sokoloff by autoradiographic and biochemical assay techniques, as are the measured kinetic rate constants of bidirectional transport, incorporation into proteins, and metabolism, as determined in monkeys and humans using L-leucine labeled with carbon-11 in position 1 (L-[1-11C]leucine) with PET. The tissue leucine precursor pool exhibits a rapid turnover rate (1.5 to 2 minutes), while the metabolic pathway has a half-time (about 18 minutes) that is close to the radioactive half-life of carbon-11. The dietary state was found to affect the branching ratio of lCRPS /metabolism, with a fasted value of 0.4 and carbohydrate feed values ranging up to 1.7. The principle of the method appears sound, and a first-order model provides good fits to data, but much more work is required to determine and validate the model structure and to optimize the study conditions and estimation criteria.