3-Tissue Compartments with Metabolites, K1/k2, Vs

If a labeled metabolite of the tracer enters tissue, the additional signal has to be accounted for in the model. The current model introduced by Fujita et al. [1] includes a second input curve C_M(t) of a metabolite entering tissue and undergoing non-specific binding. C₁ represents the non-displaceable compartment of the authentic ligand, C₂ the specific binding of interest, and C₃ metabolized ligand in tissue.

Drawing Epidepride Model

Differential Equation of the Mass Balance

with the input curves of authentic ligand and metabolite, C_p(t) and C_M(t), respectively. The input curve loading menu shows two corresponding entries as soon as the model is selected.

Operational Model Curve

with the concentration C_B(t) of tracer in whole blood, and the blood volume fraction v_B.

Parameter Fitting using K₁/k₂ and VS

The 3-Tissue Compartments with Metabolites, K1/k2, Vs model variant uses the parameter ratios K1p/k2p, K1m/k2m, K1p/K1m, and Vs=K_1p/k_2p*k₃/k₄ as fitting parameters instead of k_2p, K_1m , k_2m, and k₄. The advantage of this formulation is that the ratios may be fixed at known or assumed values, or estimated in a coupled fit. The other three fitting parameters vB, K1p and k3 are the same as for the 3-Tissue Compartments with Metabolites model.

Reference

1. Fujita M, Seibyl JP, Verhoeff NP, Ichise M, Baldwin RM, Zoghbi SS, Burger C, Staley JK, Rajeevan N, Charney DS et al: Kinetic and equilibrium analyses of [(123)I]epidepride binding to striatal and extrastriatal dopamine D(2) receptors. Synapse 1999, 34(4):290-304.