PHARMACOKINETIC MODEL OF IODINE-131-G250 ANTIBODY IN RENAL-CELL CARCINOMA PATIENTS

A model that describes the pharmacokinetic distribution of I-131-label ed G250 antibody is developed, Methods: Previously collected pharmacok inetic data from a Phase I-II study of I-131-G250 murine antibody agai nst renal cell carcinoma were used to develop a mathematical model des cribing antibody clearance from serum and the whole body, Survey meter measurements, obtained while the patient was under radiation precauti ons, and imaging data, obtained at later times, were combined to evalu ate whole-body clearance kinetics over an extended period, Results: A linear two-compartment model was found to provide good fits to the dat a. The antibody was injected into Compartment 1, the initial distribut ion volume (V-d) of the antibody, which included serum. The antibody e xchanged with the rest of the body, Compartment 2, and was eventually excreted, Data from 13 of the 16 patients fit the model with unique pa rameters; the maximum, median and minimum values for model-derived V-d were 6.3, 3.7 and 2.11, respectively. The maximum, median and minimum values for the excretion rate were 8 x 10(-2), 2.4 x 10(-2) and 1.3 x 10(-2) hr(-1), respectively, Parameter sensitivity analysis showed th at a change in the transfer rate constant from serum to the rest of th e body had the greatest effect on serum cumulative activity and that t he rate constant for excretion had the greatest effect on whole-body c umulative activity, Conclusion: A linear two-compartment model was ade quate in describing the serum and whole-body kinetics of G250 antibody distribution, The median initial distribution volume predicted by the model was consistent with the nominal value of 3.81, A wide variabili ty in fitted parameters was observed among patients, reflecting the di fferences in individual patient clearance and exchange kinetics of G25 0 antibody. By selecting median parameter values, such a model may be used to evaluate and design prolonged multiple administration radioimm unotherapy protocols.