EFFECT OF INTRAVASCULAR LIGAND-BINDING ON PARAMETER ESTIMATES DERIVEDFROM TRACER KINETIC MODELING

The purpose of this study was to assess the effect of intravascular li gand binding on parameter estimates derived from tracer kinetic modell ing. To this end intravascular ligand kinetics between the free and a bound compartment in plasma and the exchange of tracer between the cap illary space and tissue were analysed using a simple compartment model . The effect of non-equilibrated intravascular compartments on paramet er estimates was evaluated in a computer simulation. It was found that three kinetic situations must be distinguished. If the intravascular compartments are fully equilibrated when the ligand reaches the target organ, intravascular binding simply acts as a scale factor for the tr ansport-related parameter K-1. If the intravascular kinetics is very s low, only minimal binding will occur. In between there is a range wher e ongoing equilibration leads to time variability of K-1. Since tracer kinetic modelling usually does not account for such time variability, the parameter estimates become biased, the degree of the bias dependi ng on the intravascular binding kinetics. Furthermore the bias may be dependent on receptor density, meaning that model-derived receptor est imates are not linearly related to the true receptor density. It is co ncluded that intravascular ligand binding can severely affect paramete r estimates derived from tracer kinetic modelling. Especially disturbi ng are effects due to ongoing intravascular equilibration following th e arrival of the ligand in the target organ. These can be avoided by l etting the ligand equilibrate with blood in a syringe prior to injecti on.