Radioimmunotherapy of Human Colon Carcinoma Xenografts Using a 213 Bi-Labeled Domain-Deleted Humanized Monoclonal Antibody

Abstract

The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49ΔCH2) to be utilized in a radioimmunotherapeutic (RIT) application with ²¹³Bi. An initial study indicated that ¹¹¹In-HuCC49ΔCH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49ΔCH2 was then radiolabeled with ²¹³Bi, an α-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 μCi, 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 ²¹³Bi-HuCC49ΔCH2. Doses (500 μCi) 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 ²¹³Bi-HuCC49ΔCH2. As further validation of the use of ²¹³Bi-HuCC49ΔCH2 for RIT, a study using ¹³¹I was conducted. The overall survival of mice receiving ²¹³Bi-HuCC49ΔCH2 was greater than those that received ¹³¹I-HuCC49ΔCH2.