Therapeutic efficacy and dose-limiting toxicity of auger-electron vs. beta emitters in radioimmunotherapy with internalizing antibodies: Evaluation of 125I- vs. 131I-labeled CO17-1A in a human colorectal cancer model
✍ Scribed by Thomas M. Behr; George Sgouros; Vassilios Vougioukas; Stavros Memtsoudis; Stefan Gratz; Heinz Schmidberger; Rosalyn D. Blumenthal; David M. Goldenberg; Wolfgang Becker
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 187 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Recent clinical results suggest that higher anti-tumor efficacy may be achieved with internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled with Augerelectron, as compared to conventional -emitters. The aim of our study was to compare the toxicity and anti-tumor efficacy of the 125 I-labeled internalizing MAb, CO17-1A, with its 131 I-labeled form in a human colon cancer model in nude mice. Biodistribution studies were performed in nude mice bearing s.c. human colon cancer xenografts. For therapy, the mice were injected either with unlabeled 125 I-or 131 I-labeled CO17-1A at equitoxic doses. Control groups were left untreated, were given a radiolabeled isotype-matched irrelevant antibody or a tumor-specific, but noninternalizing antibody. The maximum tolerated activities (MTD) of 131 Iand 125 I-CO17-1A without artificial support were 300 µCi and 3 mCi, respectively. Myelotoxicity was dose-limiting; bone marrow transplantation allowed for an increase of the MTD to 400 µCi of 131 I-17-1A, whereas the MTD of 125 I-17-1A with bone marrow support had not been reached at 5 mCi. Whereas no significant therapeutic effects were seen with unlabeled CO17-1A, tumor growth was retarded with 131 I-CO17-1A. With the 125 I-label, however, therapeutic results were clearly superior. In contrast, no significant difference was observed in the therapeutic efficacy of the 131 I-vs. 125 I-labeled, noninternalizing antibodies. Our data indicate a superiority of Auger-electron emitters, such as 125 I, as compared to therapy with conventional -emitters with internalizing antibodies. The lower toxicity of Auger emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumor tissue, but not in the stem cells of the red marrow). Int.