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J Cereb Blood Flow Metab. 2019 Sep;39(9):1849-1863. doi: 10.1177/0271678X18771242. Epub 2018 Apr 17.

Substitution of venous for arterial blood sampling in the determination of regional rates of cerebral protein synthesis with L-[1-11C]leucine PET: A validation study.

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1 Section on Neuroadaptation & Protein Metabolism, National Institute of Mental Health, Bethesda, MD, USA.
2 Department of Neuroimaging, IoPPN, King's College London, London, UK.
3 Department of Information Engineering, University of Padova, Padova, Italy.


We developed and validated a method to estimate input functions for determination of regional rates of cerebral protein synthesis (rCPS) with L-[1-11C]leucine PET without arterial sampling. The method is based on a population-derived input function (PDIF) approach, with venous samples for calibration. Population input functions were constructed from arterial blood data measured in 25 healthy 18-24-year-old males who underwent L-[1-11C]leucine PET scans while awake. To validate the approach, three additional groups of 18-27-year-old males underwent L-[1-11C]leucine PET scans with both arterial and venous blood sampling: 13 awake healthy volunteers, 10 sedated healthy volunteers, and 5 sedated subjects with fragile X syndrome. Rate constants of the L-[1-11C]leucine kinetic model were estimated voxel-wise with measured arterial input functions and with venous-calibrated PDIFs. Venous plasma leucine measurements were used with venous-calibrated PDIFs for rCPS computation. rCPS determined with PDIFs calibrated with 30-60 min venous samples had small errors (RMSE: 4-9%), and no statistically significant differences were found in any group when compared to rCPS determined with arterial input functions. We conclude that in young adult males, PDIFs calibrated with 30-60 min venous samples can be used in place of arterial input functions for determination of rCPS with L-[1-11C]leucine PET.


Brain; leucine; positron emission tomography; protein synthesis; venous blood sampling

[Available on 2020-09-01]

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