Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody

The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49DeltaCH2) to be utilized in a radioimmunotherapeutic (RIT) application with Bi-213. An initial study indicated that In-111-HuCC49DeltaCH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49DeltaCH2 was then radiolabeled with 213 Bi, an a-emitting radionuclide with a half-life of 45.6 minutes, and evaluated for therapeutic efficacy. Dose titration studies indicated that a single dose of 500-1000 muCi, when injected by an intraperitoneal route, resulted in the growth inhibition or regression of the tumor xenograft. The radioimmunotherapeutic effect was found to be dose-dependent. Specificity of the therapeutic efficacy was confirmed in a subsequent experiment with athymic mice bearing TAG-72 negative MIP (human colorectal) xenografts. A preliminary study was also performed to assess a multiple-dose administration of Bi-213-HuCC49DeltaCH2. Doses (500 muCi) were administered at 14-day intervals after tumor implantation. A reduction in volume and/or delay in tumor growth was evident following the second and third injections of Bi-213-HuCC49DeltaCH2. As further validation of the use of Bi-213-HuCC49DeltaCH2 for RIT, a study using I-131 was conducted. The overall survival of mice receiving Bi-213-HuCC49DeltaCH2 was greater than those that received I-131-HuCC49DeltaCH2.