TY - JOUR
T1 - Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma patients
AU - Loh, Angela
AU - Sgouros, George
AU - O'Donoghue, Joseph A.
AU - Deland, Devie
AU - Puri, Dennis
AU - Capitelli, Peter
AU - Humm, John L.
AU - Larson, Steven M.
AU - Old, Lloyd J.
AU - Divgi, Chaitanya R.
PY - 1998/3
Y1 - 1998/3
N2 - A model that describes the pharmacokinetic distribution of 131I- labeled G250 antibody is developed. Methods: Previously collected pharmacokinetic data from a Phase HI study of 131I-G250 murine antibody against renal cell carcinoma were used to develop a mathematical model describing antibody clearance from serum and the whole body. Survey meter measurements, obtained while the patient was under radiation precautions, and imaging data, obtained at later times, were combined to evaluate whole-body clearance kinetics over an extended period. Results: A linear two-compartment model was found to provide good fits to the data. The antibody was injected into Compartment 1, the initial distribution volume (V(d)) of the antibody, which included serum. The antibody exchange with the rest of the body, Compartment 2, and was eventually excreted. Data from 13 of the 16 patients fit the model with unique parameters; 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 that a change in the transfer rate constant from serum to the rest of the body had the greatest effect on serum cumulative activity and that the rate constant for excretion had the greatest effect on whole-body cumulative activity. Conclusion: A linear two-compartment model was adequate 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 variability in fitted parameters was observed among patients, reflecting the differences in individual patient clearance and exchange kinetics of G250 antibody. By selecting median parameter values, such a model may be used to evaluate and design prolonged multiple administration radioimmunotherapy protocols.
AB - A model that describes the pharmacokinetic distribution of 131I- labeled G250 antibody is developed. Methods: Previously collected pharmacokinetic data from a Phase HI study of 131I-G250 murine antibody against renal cell carcinoma were used to develop a mathematical model describing antibody clearance from serum and the whole body. Survey meter measurements, obtained while the patient was under radiation precautions, and imaging data, obtained at later times, were combined to evaluate whole-body clearance kinetics over an extended period. Results: A linear two-compartment model was found to provide good fits to the data. The antibody was injected into Compartment 1, the initial distribution volume (V(d)) of the antibody, which included serum. The antibody exchange with the rest of the body, Compartment 2, and was eventually excreted. Data from 13 of the 16 patients fit the model with unique parameters; 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 that a change in the transfer rate constant from serum to the rest of the body had the greatest effect on serum cumulative activity and that the rate constant for excretion had the greatest effect on whole-body cumulative activity. Conclusion: A linear two-compartment model was adequate 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 variability in fitted parameters was observed among patients, reflecting the differences in individual patient clearance and exchange kinetics of G250 antibody. By selecting median parameter values, such a model may be used to evaluate and design prolonged multiple administration radioimmunotherapy protocols.
KW - Antibody
KW - Modeling
KW - Pharmacokinetics
KW - Radioimmunotherapy
KW - Treatment planning
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M3 - Article
C2 - 9529296
AN - SCOPUS:0031905826
SN - 0161-5505
VL - 39
SP - 484
EP - 489
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -