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Processing of antibody‐radioisotope conjugates after binding to the surface of tumor cells
Author(s) -
Jules Mattes M.,
Griffiths Gary L.,
Diril Habibe,
Goldenberg David M.,
Ong Gaik Lin,
Shih Lisa B.
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940201)73:3+<787::aid-cncr2820731307>3.0.co;2-5
Subject(s) - antibody , antigen , catabolism , in vitro , biochemistry , cell , microbiology and biotechnology , chemistry , metabolism , biology , immunology
Background . Previous experiments indicated that most antibodies binding to cell surface antigens are internalized gradually and degraded within lysosomes, with a half‐life of degradation of approximately 1 day, for most antibodies. The research discussed in this article extended our studies to eight additional antibodies reacting with six different antigens, including three antigens anchored in the membrane by glycosyl‐phosphatidylinositol. The authors also tested antibodies labeled with 111 indium, as well as 125 iodine, to determine whether different radiolabels would be processed differently. Methods . Antibodies were radiolabeled with 125 I or with 111 In bound to benzyl‐DTPA. After binding to the surface of tumor cells in vitro, excess antibody was washed away, and the fate of the radiolabel was investigated over periods of 3–7 days. Radiolabel released into the supernatant or retained by the cells was analyzed to determine whether it was still on intact antibody. Results . In 13 of the 15 antibodies that were tested, a similar pattern of irreversible binding and gradual catabolism was observed. Iodine conjugated to antibodies was released rapidly from the cell after antibody catabolism. In contrast, the 111 In was retained within the cell much longer than 125 I, with the rate of degradation and release into the medium being at least fivefold slower. More than 50% of the bound 111 In was still present on the cells after 7 days. Biochemical analysis of the retained 111 In extracted cells after 4–6 days demonstrated that it was no longer associated with antibodies and was in a low molecular weight form, probably still associated with the chelator benzyl‐DTPA. Conclusions . Different radiolabels are processed by tumor cells differently, after catabolism of the antibody to which they originally were conjugated. The data suggest that the prolonged retention of 111 In, relative to that of 125 I, is due not to deiodination of iodine conjugates, but rather to intracellular retention of catabolic products containing 111 In, perhaps within lysosomes. The use of radioisotopes that are retained within cells after antibody internalization and degradation may improve both radioimmunodetection and radioimmunotherapy of cancer. Cancer 1994; 73:787–93.