Measurement of regional rates of cerebral protein synthesis with L-[1-11C]leucine and PET with correction for recycling of tissue amino acids: I. Kinetic modeling approach

Abstract

Measurements of regional rates of cerebral protein synthesis (rCPS) require correction for the effect of recycling of tissue amino acids back into the precursor pool for protein synthesis. The fraction of the precursor pool derived from arterial plasma, lambda, can be evaluated as the steady-state ratio of the specific activity of leucine in the tissue tRNA-bound fraction to that in arterial plasma. While lambda can be directly measured in terminal experiments in animals, an alternative method is required for use with PET. We report a method to estimate lambda based on a kinetic model of labeled and unlabeled leucine and labeled CO2 in the tissue. The kinetic model is also used to estimate the amount of labeled protein and rCPS. We measured time courses of [14C]leucine, [14C]protein, and 14CO2 in the blood and brain of anesthetized rats and estimated parameters of the kinetic model from these data. Simulation studies based on the kinetic parameters were then performed to examine the feasibility of this approach for use with L-[1-11C]leucine and PET. Lambda and rCPS were estimated with low bias, which suggests that PET can be used for quantitative measurement of rCPS with L-[1-11C]leucine and a kinetic modeling approach for correction for recycling of tissue amino acids.