Abstract:Purpose: Knowledge of the blood pharmacokinetics of monoclonal antibodies is crucial in deciding the optimal time for starting the administration of a “clearing agent” or using a “clearing device.” The primary purpose was to investigate whether the pharmacokinetics of various antibodies labeled with the same chelator and 111In differed significantly after i.v. injection in immunocompetent rats. A new trifunctional chelator called “1033” containing a biotin and a radiometal chelation moiety is introduced, making it possible to use only one conjugation procedure for the antibody.Experimental Design: Sixty-five non–tumor-bearing rats were included and divided into four groups (I-IV). The blood pharmacokinetics was investigated for rituximab, BR96, and trastuzumab labeled with 1033 and 111In (I-III). The whole-body activity and activity uptake in muscle, liver, and kidney, which might explain differences in the early pharmacokinetics in blood, were also measured. hMN14 labeled with another chelator [1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)], but with the same radionuclide (111In-biotin-DOTA-hMN14), was studied (IV). The blood pharmacokinetics from another 15 tumor-bearing rats was compared with those of non–tumor-bearing rats (III) by injection of 111In-1033-BR96.Results: No statistical difference was detected between the groups regarding the blood pharmacokinetics of rituximab, BR96, or trastuzumab. The pharmacokinetics and biodistribution of 111In-biotin-DOTA-hMN14 exhibited a clear difference compared with others. There were no significant differences in the blood pharmacokinetics of 111In-1033-BR96 between tumor-bearing rats and non–tumor-bearing rats.Conclusions: Different antibodies labeled with the trifunctional chelator 1033 and 111In did not exhibit different blood pharmacokinetics, which means that the pharmacokinetics could be predicted irrespective of the IgG1 antibody chosen. A small tumor burden did not change the pharmacokinetics of the radioimmunoconjugates.