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Center for Molecular Medicine and Immunology at the Garden State Cancer Center and Immunomedics, Inc., Newark, New Jersey
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina
Correspondence: For correspondence or reprints contact: Dr. M.J. Mattes, Center for Molecular Medicine and Immunology, 1 Bruce St., Newark, NJ 07103.
ABSTRACT
Processing radiolabeled degradation products is the key factor affecting retention of antibodies with in the cell. In this study, we have analyzed the processing of antibodies labeled in nine different ways. Methods: Antibodies were labeled with three different radioisotopes and seven different forms of 125I. Eight of the radiolabels (except 186Re) were conjugated to the same antibody, MA103, and tested on the renal carcinoma cell line SK-RC-18 and/or the ovarian carcinoma cell line SK-OV-6. Rhenium conjugation utilized the antibody RS7, the target cell line ME180 and three of the other radiolabels were also tested with this antibody-target cell combination for comparison. Results: Iodine conjugated to antibodies by conventional methods was rapidly released from the cell after antibody catabolism. In contrast, iodinated moieties, such as dilactitol-tyramine and inulin-tyramine were retained within cells four to five times longer. Conclusions: The use of radiolabels that are trapped within cells after antibody catabolism can potentially increase the dose of radiation delivered to the tumor, from the same amount of radioactivity deposited by a factor of four or five. The prolonged retention of 111In relative to 125I is not due to deiodination of iodine conjugates, but rather to intracellular retention of catabolic products containing 111In, perhaps within lysosomes.
Key Words: antibody conjugates • radioimmunotherapy • catabolism of radioisotope conjugates
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