GOODNESS-OF-FIT AND LOCAL IDENTIFIABILITY OF A RECEPTOR-BINDING RADIOPHARMACOKINETIC SYSTEM

A four-state nonlinear model describing a radiopharmacokinetic system for a hepatic receptor-binding radiopharmaceutical, [Tc-99m]-galactosy l-neoglycoalbumin (TcNGA), was tested for goodness-of-fit and local id entifiability using scanning data from nine healthy subjects and seven patients with severe liver disease. Based on standard deviations of l iver and heart imaging data at equilibria as a measure of observationa l error, the reduced chi-square ranged from 0.5 to 2.6. Values above 1 .2 occurred when the subject moved during the 30 min study. Relative s tandard errors for each parameter were: TcNGA-receptor forward binding rate constant k(b), 13-54%; extra-hepatic plasma volume V(e), 0.8-15. 0%; hepatic plasma volume V(h), 0.2-6.5%; hepatic plasma flow F, 54 -- > > 1000%; and receptor concentration [R]o, 0.3-13%. The highest stand ard errors occurred when the amount of TcNGA injected exceeded the tot al amount of receptor. Therefore, when TcNGA functional imaging was pe rformed without excess patient motion and receptor saturation, the kin etic model provided data fits of low systematic error and yielded high precision estimates of receptor concentration and forward binding rat e constant. In summary, optimal performance of the kinetic model occur red when the amount ot' injected TcNGA resulted in the nonlinear opera tion of the pharmacokinetic system.