Fig 1. (A) Homogeneous Tissue Model for L-[1-¹¹C]Leucine PET method.

Top rows illustrate the model used to describe the behaviour of labeled leucine in brain. K₁ and k₂ are the rate constants for transport of leucine from plasma to tissue and back, respectively. k₃ is the rate constant for the first two steps in leucine catabolism, transamination and decarboxylation, which yields ¹¹CO₂. k₄ and k₅ are the rate constants for leucine incorporation into protein and for the release of free leucine from proteolysis, respectively. Because of the long half-life of protein in brain (Lajtha et al, 1976), it is assumed that there is no significant breakdown of labeled product (P*) during the experimental interval, i.e., k₅P*~0. Labeled CO₂ arises either through catabolism of labeled leucine in brain or through influx from blood after catabolism in other tissue, and once in brain it may be either transported back to blood or fixed in brain. Assuming no isotope effect, the rate constants for labeled and unlabeled leucine are identical. Thus the model used to describe labeled leucine holds also for unlabeled leucine (bottom part of the figure), except that unlabeled leucine and protein are in steady state, and the steady-state breakdown of unlabeled protein, k₅P, is greater than zero. The model assumes that the tissue is homogeneous with respect to concentrations of amino acids, blood flow, rates of transport and metabolism of amino acids, and rates of incorporation into protein. From Schmidt et al, 2005.

(B) Simplified Homogeneous Tissue Model. Under the assumptions of negligible fixation of ¹¹CO₂ during the experimental period (Siesjo and Thompson, 1965) and rapid equilibration of ¹¹CO₂ between brain and blood (Buxton et al, 1987), the model reduces to two tissue compartments (C_E* and P*) plus the ¹¹ CO₂ compartment in which the concentration is known.