Comparative radiolabeling and distribution of a tumour-directed monoclonal antibody.
The monoclonal antibody (MAb) 155H.7, raised against a synthetic beta-anomer of the Thomsen-Friedenreich antigen (S-TAG), was radioiodinated using iodine monochloride, chloramine-T and Iodogen and radiolabeled with 111In using the bromoacetamido-derivative of benzyl-EDTA. The in vitro immunoreactivity of the MAb was assessed using an ELISA with the S-TAG and the in vivo distribution of the radioiodinated and radiochelated MAb was determined in the murine mammary carcinoma TA3/Ha tumour model. Both chloramine-T and iodine monochloride radioiodination greatly reduced the immunoreactivity of the MAb compared to radioiodination using Iodogen. Bifunctional chelate labeling was comparable to Iodogen in reducing the immunoreactivity of the MAb and subsequent chelation of 111In did not further compromise the immunoreactivity of the MAb. The in vivo distribution data showed significantly different distributions of the radiolabels after injection of the radioiodinated and radiochelated MAb. The 131I-MAb showed some tumour association as compared to the distribution of an 125I-non-specific protein and the data also indicates that there is preferential dehalogenation of the radioiodinated MAb. 111In from the radiochelated MAb showed significantly higher uptake in the tumour than 131I from the 131I-MAb. It is suggested that the differing fates of the two radiolabels within the tumour cell is responsible for the difference in retention observed and not necessarily due to the lack of MAb uptake by the tumour. Overall, the radiochelate label for MAb 155H.7 appears to be superior to radioiodine for in vivo use.
Turner
C J
CJ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Sykes
T R
TR
Longenecker
B M
BM
Noujaim
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides / Q000276:immunology; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging; D051379:Mice; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; C016467:Thomsen-Friedenreich antigen