Measurement of Protein Synthesis Rate in Rat by [ 11 C]Leucine PET Imaging: Application to the TgF344-AD Model of Alzheimer’s Disease

Long-term memory requires stable protein synthesis and is altered in Alzheimer’s disease (AD). This study aimed to implement a method to measure the cerebral protein synthesis rate (PSR) with [ 11 C]leucine PET in vivo in rats and evaluate potential PSR alterations longitudinally (6, 12 and 18 months old) in the TgF344-AD rat model of AD. Wistar, wild-type (WT) and TgF344-AD rats (TG) were scanned for 60 min with [ 11 C]leucine. Arterial blood activity was monitored online and with discrete whole blood and plasma samples by γ-counting in Wistar rats, WT ( n = 4) and TG ( n = 5). Unlabelled amino acids were measured in plasma. The sensitivity of [ 11 C]leucine PET to measure alterations in PSR was assessed in Wistar rats by injection of PSR inhibitor anisomycin before PET acquisition. Anisomycin administration significantly reduced the net uptake rate constant ( K cplx ) of [ 11 C]leucine and PSR, proving the suitability of the method. For the longitudinal study, averaged population-based input functions were used to calculate PSR. We found a significant genotype effect on PSR (decrease in TG vs WT) only in the globus pallidus. This study suggests that [ 11 C]leucine PET is sensitive enough to measure brain PSR in rat but that cross-sectional design with individual input function should be preferred.