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

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.