The processing and fate of antibodies and their radiolabels bound to the surface of tumor cells in vitro: a comparison of nine radiolabels.
Processing radiolabeled degradation products is the key factor affecting retention of antibodies within 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 188Re) 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.
Shih
L B
LB
Center for Molecular Medicine and Immunology, Garden State Cancer Center, Newark, New Jersey.
Thorpe
S R
SR
Griffiths
G L
GL
Diril
H
H
Ong
G L
GL
Hansen
H J
HJ
Goldenberg
D M
DM
Mattes
M J
MJ
D000116:Acetylgalactosamine / Q000031:analogs & derivatives; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D005260:Female; D007205:Indium Radioisotopes / Q000378:metabolism* / Q000627:therapeutic use; D007444:Inulin / Q000031:analogs & derivatives; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000378:metabolism* / Q000627:therapeutic use; D012211:Rhenium / Q000378:metabolism* / Q000627:therapeutic use; D012710:Serum Albumin, Bovine; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; C079431:N-acetylgalactosamine-bovine serum albumin conjugate; D011868:Radioisotopes; C057271:inulin-tyramine; D012710:Serum Albumin, Bovine; D012211:Rhenium; D007444:Inulin; C049133:dilactitol tyramine; D000116:Acetylgalactosamine; D014439:Tyramine