Bishu Shrinivas, Schmidt Kathleen C, Burlin Thomas, Channing Michael, Conant Shielah, Huang Tianjiang, Liu Zhong-hua, Qin Mei, Unterman Aaron, Xia Zengyan, Zametkin Alan, Herscovitch Peter, Smith Carolyn B
Section on Neuroadaptation & Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1298, USA.
J Cereb Blood Flow Metab. 2008 Aug;28(8):1502-13. doi: 10.1038/jcbfm.2008.43. Epub 2008 May 21.
We report regional rates of cerebral protein synthesis (rCPS) measured with the fully quantitative L-[1-(11)C]leucine positron emission tomography (PET) method. The method accounts for the fraction (lambda) of unlabeled amino acids in the precursor pool for protein synthesis derived from arterial plasma; the remainder (1-lambda) comes from tissue proteolysis. We determined rCPS and lambda in 18 regions and whole brain in 10 healthy men (21 to 24 years). Subjects underwent two 90-min dynamic PET studies with arterial blood sampling at least 2 weeks apart. Rates of cerebral protein synthesis varied regionally and ranged from 0.97+/-0.70 to 2.25+/-0.20 nmol/g per min. Values of rCPS were in good agreement between the two PET studies. Mean differences in rCPS between studies ranged from 9% in cortical regions to 15% in white matter. The lambda value was comparatively more uniform across regions, ranging from 0.63+/-0.03 to 0.79+/-0.02. Mean differences in lambda between studies were 2% to 8%. Intersubject variability in rCPS was on average 6% in cortical areas, 9% in subcortical regions, and 12% in white matter; intersubject variability in lambda was 2% to 8%. Our data indicate that in human subjects low variance and highly reproducible measures of rCPS can be made with the L-[1-(11)C]leucine PET method.
我们报告了采用完全定量的L-[1-(11)C]亮氨酸正电子发射断层扫描(PET)方法测量的脑蛋白合成区域速率(rCPS)。该方法考虑了来自动脉血浆的蛋白质合成前体库中未标记氨基酸的比例(λ);其余部分(1-λ)来自组织蛋白水解。我们在10名健康男性(21至24岁)的18个脑区和全脑中测定了rCPS和λ。受试者相隔至少2周接受了两次90分钟的动态PET研究,并采集动脉血样。脑蛋白合成速率存在区域差异,范围为0.97±0.70至2.25±0.20 nmol/g每分钟。两次PET研究中rCPS的值吻合良好。研究之间rCPS的平均差异在皮质区域为9%,在白质区域为15%。λ值在各区域相对更均匀,范围为0.63±0.03至0.79±0.02。研究之间λ的平均差异为2%至8%。rCPS的受试者间变异性在皮质区域平均为6%,在皮质下区域为9%,在白质区域为12%;λ的受试者间变异性为2%至8%。我们的数据表明,在人类受试者中,使用L-[1-(11)C]亮氨酸PET方法可以获得低方差且高度可重复的rCPS测量值。