title: Dependence of the anti-CD66 antibody biodistribution on the dissociation constant: a simulation study.
abstract: In radioimmunotherapy (RIT) with radiolabelled anti-CD66 antibody, the red bone marrow is selectively irradiated. A preceding study, employing a physiologically based pharmacokinetic model, has shown that currently about 50% of the anti-CD66 antibody is accumulated in the red marrow. In this work, the potential improvement of the biodistribution is quantified for other anti-CD66 antibodies with lower dissociation constants K(D). Biodistribution simulations were performed based on a recently published mathematical model for a 10- and 100-fold lower monovalent K(D). The therapeutic index was compared to the therapeutic index which is achieved using the actual antibody. The simulations indicate that a considerably increased therapeutic index can be obtained by decreasing the dissociation constant.A reduction of the K(D) to 10-fold or 100-fold lower values would lead to an improvement of the therapeutic index, by a factor of 2.4-5 and 2.4-6.5 respectively. To investigate the predicted improvement of the radioimmunotherapy, new anti-CD66 antibodies with lower dissociation constants should be developed.
authors.affiliation: Klinik für Nuklearmedizin, Universität Ulm, Germany. peter.kletting@uniklinik-ulm.de
authors.forename: Peter
authors.initials: P
authors.lastname: Kletting
authors.forename: Sven N
authors.initials: SN
authors.lastname: Reske
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000097:blood*; D015703:Antigens, CD / Q000276:immunology*; D001853:Bone Marrow / Q000528:radiation effects*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003198:Computer Simulation; D006801:Humans; D007158:Immunologic Techniques; D008962:Models, Theoretical; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D015021:Yttrium Radioisotopes