OBJECTIVE: Monoclonal antibody (mAb)-based radioimmunoconjugates (RICs) exhibit marked tumor uptake in cancer imaging and therapy, although their high blood retention has limited the development of RICs. In our previous study, a trifunctional chelating agent with a cationic poly(ethyleneimine) (PEI) structure of tetraethylenepentamine (PEI4), maleimide-DOTA-PEI4 (MDI4), improved the tumor-to-blood ratio of RICs by increasing tumor retention compared with a conventional bifunctional chelating agent. In this study, we developed a novel chelating agent composed of a maleimide moiety, DOTA derivative, and two PEI4 structures as a PEI4-2 unit, maleimide-DOTA-PEI4-2 (MDI4-2), a design for a highly cationized chelating agent to synthesize RICs. The properties of MDI4-2 were compared with MDI4 to evaluate the effect of the PEI4-2 unit on the pharmacokinetics of RICs. METHODS: Trastuzumab and RESULTS: [ CONCLUSION: MDI4-2 with the PEI4-2 unit exhibited favorable properties for designing RICs with an improved tumor-to-blood ratio.