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Therapeutic efficacy and dose‐limiting toxicity of auger‐electron vs . beta emitters in radioimmunotherapy with internalizing antibodies: Evaluation of 125 I‐ vs . 131 I‐labeled CO17‐1A in a human colorectal cancer model
Author(s) -
Behr Thomas M.,
Sgouros George,
Vougioukas Vassilios,
Memtsoudis Stavros,
Gratz Stefan,
Schmidberger Heinz,
Blumenthal Rosalyn D.,
Goldenberg David M.,
Becker Wolfgang
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980529)76:5<738::aid-ijc20>3.0.co;2-z
Subject(s) - radioimmunotherapy , medicine , limiting , toxicity , oncology , cancer research , chemistry , antibody , monoclonal antibody , immunology , mechanical engineering , engineering
Recent clinical results suggest that higher anti‐tumor efficacy may be achieved with internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled with Auger‐electron, as compared to conventional β‐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 I‐ and 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 β‐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. J. Cancer 76:738–748, 1998.© 1998 Wiley‐Liss, Inc.