Determination of the immunoreactivity of radiolabeled monoclonal antibodies: a theoretical analysis.
Conjugates of monoclonal antibodies with radioactive nuclides are frequently used in radioimmunotherapy. Because the conjugation procedure may adversely alter the antibody, the immunoreactivity of the antibody must be determined. In this study, we expand the mathematical description of cell-binding assays for the determination of immunoreactivity to include the amount of unlabeled antibody. We describe the relevant equations and constraints and develop a mathematical description of the underlying measurements. The dependence on antibody, on antigen or cell concentration, on the dissociation constant, and on the specific activity is taken into account. The functional dependence of bound labeled antibody on the experimental parameters is given, and the consequences for parameter estimation are discussed. In order to correctly interpret the experimental data for the immunoreactivity, one requires a mathematical model without unnecessary assumptions together with an appropriate nonlinear regression fit.
Glatting
Gerhard
G
Abteilung Nuklearmedizin, Universität Ulm, Ulm, Germany. gerhard.glatting@uniklinik-ulm.de
Reske
Sven N
SN
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000493:pharmacokinetics; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D011868:Radioisotopes