¹Unit on Neuroadaptation and Protein Metabolism, Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: KC Schmidt, Unit on Neuroadaptation and Protein Metabolism, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bldg 36, Rm 1A07, 36 Convent Drive, Bethesda, MD 20892-4030, USA. E-mail: SchmidtK@intra.nimh.nih.gov

Received 1 July 2004; Revised 14 September 2004; Accepted 5 October 2004; Published online 9 February 2005.

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, , 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 can be directly measured in terminal experiments in animals, an alternative method is required for use with PET. We report a method to estimate 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. 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.