Measurement of Regional Rates of Cerebral Protein Synthesis with L-[1-11C]leucine and PET with Correction for Recycling of Tissue Amino Acids: II. Validation in Rhesus Monkeys

• Published in: Journal of cerebral blood flow and metabolism 2005-05, Vol.25 (5), p.629-640
• Main Authors: Smith, Carolyn Beebe, Schmidt, Kathleen C, Qin, Mei, Burlin, Thomas V, Cook, Michelle P, Kang, Julia, Saunders, Richard C, Bacher, John D, Carson, Richard E, Channing, Michael A, Eckelman, William C, Herscovitch, Peter, Laverman, Peter, Vuong, Bik-Kee
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Animals; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Brain - metabolism; Carbon Radioisotopes - analysis; Carbon Radioisotopes - metabolism; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Kinetics; Leucine - analysis; Leucine - metabolism; Macaca mulatta; Male; Medical sciences; Models, Neurological; Nervous system (semeiology, syndromes); Neurology; Pharmacology. Drug treatments; Positron-Emission Tomography; Protein Biosynthesis - physiology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600066

The confounding effect of recycling of amino acids derived from tissue protein breakdown into the precursor pool for protein synthesis has been an obstacle to adapting in vivo methods for determination of regional rates of cerebral protein synthesis (rCPS) to positron emission tomography (PET). We used a kinetic modeling approach to estimate λ, the fraction of the precursor pool for protein synthesis derived from arterial plasma, and to measure rCPS in three anesthetized adult monkeys dynamically scanned after a bolus injection of L-[1-11C]leucine. In the same animals, λ was directly measured in a steady-state terminal experiment, and values showed excellent agreement with those estimated in the PET studies. In three additional monkeys rCPS was determined with the quantitative autoradiographic L-[1-14C]leucine method. In whole brain and cerebellum, rates of protein synthesis determined with the autoradiographic method were in excellent agreement with those determined with PET, and regional values were in good agreement when differences in spatial resolution of the two methods were taken into account. Low intrasubject variability was found on repeated PET studies. Our results in anesthetized monkey indicate that, by using a kinetic modeling approach to correct for recycling of tissue amino acids, quantitatively accurate and reproducible measurement of rCPS is possible with L-[1-11C]leucine and PET.