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.
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 lambda, 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, lambda 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.
Smith
Carolyn Beebe
CB
Unit on Neuroadaptation and Protein Metabolism, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892-4030, USA. beebec@intra.nimh.nih.gov
Schmidt
Kathleen C
KC
Qin
Mei
M
Burlin
Thomas V
TV
Cook
Michelle P
MP
Kang
Julia
J
Saunders
Richard C
RC
Bacher
John D
JD
Carson
Richard E
RE
Channing
Michael A
MA
Eckelman
William C
WC
Herscovitch
Peter
P
Laverman
Peter
P
Vuong
Bik-Kee
BK
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000032:analysis / Q000378:metabolism; D005260:Female; D007700:Kinetics; D007930:Leucine / Q000032:analysis / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008959:Models, Neurological; D049268:Positron-Emission Tomography; D014176:Protein Biosynthesis / Q000502:physiology*
D000596:Amino Acids; D002250:Carbon Radioisotopes; D007930:Leucine