Dependence of the anti-CD66 antibody biodistribution on the dissociation constant: a simulation study

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.