Two-tissue compartment model with blood input function. As shown in Figure 1, the compartments represent CFN that is free in tissue and bound to receptors. The model contains 4 parameters (K1-k4), with the binding potential being equal to k3/k4. It is difficult to estimate all parameters simultaneously thus parameter estimation is performed in two steps. First, the distribution volume in occipital cortex (OCC) is estimated using either a one-compartment or two-compartment model. Because OCC is relatively devoid of mu-opioid receptors, the OCC distribution volume is expected to be nearly equal to the free volume of distribution (K1/k2) in receptor-rich areas. Thus K1/k2 in all other regions will be constrained to the OCC distribution volume.
Here is an example of fitting a CFN time-activity curve (caudate) to a two-compartment model. We have found in our studies that the two-compartment model is sufficient to describe CFN kinetics.