Radioimmunotherapy (RIT) with anti-CD45 antibody: Optimal timing of the preload

1632 Objectives The amount of unlabeled antibody is an important factor in achieving the optimal biodistribution for RIT using anti-CD45 antibody. Furthermore, it has been demonstrated that the time delay Δt between the administration of labeled and unlabeled antibody is of considerable importance. In this work, the Δt leading to the most favorable biodistribution is determined. Methods To investigate the optimal Δt a physiologically based pharmacokinetic model (PBPK) model and biokinetic data (N=5) were used. The patients received a preload of 0.5 mg/kg unlabeled antibody 16-34 min before the application of 1 mg ln-111 labeled antibody (121±21MBq). Based on the individually estimated biokinetic parameters of the PBPK model, the biodistributions for various Δt (0–120 min) were simulated. The residence times tau of the critical organs liver, spleen, red marrow (RM) and blood were determined. The most favorable distribution was defined as being the maximum of tauRM/tauLiver. Results The optimal Δt for all five patients was identified. The best biodistribution was achieved by administering the labeled antibody 5 min (range 0-10 min) after the preload. Interestingly, the best Δt is decreasing with an increasing ratio of antibody to antigen from 10 to 0 min. The ratio tauRM/tauLiver could be improved by a factor of 1.3 (range 1.2-1.6) Conclusions The results indicate that the optimal timing depends on the antibodies to antigens ratio of each patient. Therefore, the amount of unlabelled antibody and the Δt has to be determined individually. The optimal timing and dosing of the preload could significantly improve RIT with anti-CD45 antibody. Research Support German research foundation (DFG GL 236/7-1).