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Multicompartmental Analysis of the Kinetics of Radioiodinated Monoclonal Antibody in Patients with Cancer

Department of Nuclear Medicine, Kanazawa University School of Medicine, Kanazawa, Japan
Division of Nuclear Medicine, University of California Davis Medical Center, Sacramento, California
Research and Development, Veterans Administration Medical Center, Palo Alto, California
Advanced Technology, ADAC Laboratories, San Jose, California
Advanced Technology, Sterling Networks, Inc., Redwood City, California

Correspondence: For reprints contact: Gerald L. DeNardo, MD, Div. of Nuclear Medicine, 4301 X St., FOLB II-E, University of California Davis Medical Center, Sacramento, CA 95817.

ABSTRACT

A conceptual biologic model was developed and used to analyze the behavior of ¹²³I-Lym-1 monoclonal antibody against African human B cell lymphoma in patients with B cell lymphoma. Originally, the observed data could not be simulated with parameters for homologous immunoglobulins reported in the literature because of a major processor that was capable of distinguishing this murine immunoglobulin from the patient's own immunoglobulins. With a nonlinear parametric model, the data observed in patients could be fitted to the model. The nonlinear parameter determined the transfer of antibody from the intravascular to a processor compartment, primarily the liver. This transfer was a function of the number of free receptors in the processor. Model simulated curves for the time course of concentration of antibody in the blood for different amounts of injected antibody revealed that blood clearance of radiolabeled antibody was profoundly decreased by increased amount of injected antibody. This model provides an explanation for the observations that tumor imaging is improved with injection of larger amounts of antibody, and a basis for modifying the pharmacokinetic behavior of an antibody in order to optimize radioimmunodiagnosis and radioimmunotherapy.