Cure of metastatic human colonic cancer in mice with radiolabeled monoclonal antibody fragments.
There is currently no method to cure patients with disseminated colorectal cancer, which is the third leading cancer killer in the Western World. This report shows that the GW-39 intrapulmonary micrometastatic human colonic cancer model in nude mice can be cured with radiolabeled antibodies against carcinoembryonic antigen, and that this approach of radioimmunotherapy is superior to conventional chemotherapy with 5-fluorouracil and leucovorin (5-FU/LV). Monovalent Fab fragments labeled with 131I are superior to intact IgG when survival was evaluated 3, 7, and 14 days after implantation, leading to cures in up to 90% of the mice. Histological results provide support for the differences in therapeutic efficacy observed. Microautoradiography was used to evaluate the intratumoral distribution of each form of antibody. The enhanced tumor control by Fab compared with IgG could be explained in part by the homogeneity of radioantibody distribution of Fab. Biodistribution analysis and initial dose rate calculations for all three forms of antibody also help explain the ability of 131I-labeled Fab to provide better tumor growth control than seen with 131I-labeled IgG. Thus, radioimmunotherapy may be a new modality to treat metastatic disease, particularly when using small antibody fragments.
Behr
T M
TM
Department of Nuclear Medicine of the Georg-August-University, Göttingen, Germany.
Blumenthal
R D
RD
Memtsoudis
S
S
Sharkey
R M
RM
Gratz
S
S
Becker
W
W
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002272:Carcinoembryonic Antigen / Q000276:immunology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D002955:Leucovorin / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011874:Radiometry; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D002955:Leucovorin; D005472:Fluorouracil