Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases.
Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.
Mahteme
H
H
Department of Surgery, Uppsala University, Sweden.
Lövqvist
A
A
Graf
W
W
Lundqvist
H
H
Carlsson
J
J
Sundin
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001835:Body Weight; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D016499:Radioimmunotherapy; D051381:Rats
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes