Measurement of regional rates of cerebral protein synthesis with L-[1-¹¹C]leucine and PET with correction for recycling of tissue amino acids: Optimal scanning interval

Abstract

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Objectives: We have validated in monkeys a method for quantitative determination of regional rates of cerebral protein synthesis (rCPS) with L-[1-¹¹C]leucine and PET (Smith et al., JCBFM 2005; 25:629-40). The method uses a kinetic modeling approach to estimate λ, the fraction of the precursor pool for protein synthesis derived from arterial plasma, in order to correct for recycling of tissue amino acids (Schmidt et al., JCBFM 2005; 25:617-28). Because estimates of kinetic model rate constants decline with time in heterogeneous tissues until all precursor pools equilibrate with arterial plasma (Schmidt et al., JCBFM 1991; 11:10-24), calculated rCPS may also change with time until equilibrium has been achieved. The present study was undertaken to determine the best scanning interval for determination of rCPS.

Methods: Anesthetized monkeys were dynamically scanned for 60 min following injection of L-[1-¹¹C]leucine. ROIs were placed on MR images and transferred to co-registered PET images to construct tissue time activity curves. Nine studies were performed. Kinetic model rate constants and λ were estimated over varying time intervals for whole brain and 6 ROIs. rCPS was computed as rCPS=[(K₁k₄)/(k₂+k₃+k₄)](Cp/λ) where Cp is the arterial plasma leucine concentration. K₁-k₄ are rate constants for transport of leucine from plasma to brain, from brain to plasma, for catabolism of leucine, and for incorporation of leucine into protein, respectively. The Spearman rank-order correlation coefficient, r_s, was used to test whether trends in the estimated rate constants and rCPS were statistically significant.

Results: Rate constants and rCPS (table) in 8/9 whole brain volumes and in 39-41% of ROIs showed perfect rank-order correlation of decreasing values with increasing time (r_s=1, p<10^–6). Increasing estimates with increasing time were found in 7% of ROIs (r_s=–1, p<10^–6). Trends in the remaining ROIs were not statistically significant.

Conclusions: The scanning interval for determination of rCPS should not be shorter than 60 min. As evidence of leveling off of rCPS estimates in all regions was not yet seen, additional studies with longer scanning intervals are underway to identify the optimal scanning time.