Regional Rates of Cerebral Protein Synthesis Measured with l-[1-¹¹C]Leucine and PET in Conscious, Young Adult Men: Normal Values, Variability, and Reproducibility

Abstract

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.

Voxel-Based Estimation of Kinetic Model Parameters of the l-[1-11C]Leucine PET Method for Determination of Regional Rates of Cerebral Protein Synthesis: Validation and Comparison with Region-of-Interest-Based Methods

“…The criteria for subject inclusion and the procedure for L-[1- 11 C]leucine PET studies are described in detail in Bishu et al (2008). All studies were performed on the ECAT High Resolution Research Tomograph (HRRT) (CPS Innovations, Knoxville, TN), which has a spatial resolution of ~2.6 mm full width at half maximum (FWHM) (Weinhard et al, 2002).…”

“…We have implemented the method in awake, healthy young men and demonstrated that reproducible measurements of rCPS with low variability can be obtained (Bishu et al, 2008). Future applications are expected in studies of normal human brain, neurodegenerative diseases, and neurodevelopmental disorders that might be associated with dysregulation of cerebral protein synthesis (Bear et al, 2008).…”

The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

“…Finally, similar measurements performed in the KO mouse in vivo show a global increase in brain protein synthesis (Qin et al 2005). The fact that increased protein synthesis can be observed in the intact animal in vivo has raised the possibility that measurements of protein synthesis could serve as a biomarker of disease (Bishu et al 2008, Bishu et al 2009). Indeed, studies are currently underway to test this hypothesis in human patients with FX (http://www.clinicaltrials.gov).…”

Propofol Anesthesia Does Not Alter Regional Rates of Cerebral Protein Synthesis Measured withl-[1-11C]Leucine and PET in Healthy Male Subjects

“…We have recently implemented the method in awake, healthy young men and demonstrated that reproducible measurements of rCPS with low variability can be obtained (Bishu et al 2008). …”