RHENIUM-186-MERCAPTOACETYLTRIGLYCINE-LABELED MONOCLONAL-ANTIBODY FOR RADIOIMMUNOTHERAPY - IN-VITRO ASSESSMENT, IN-VIVO KINETICS AND DOSIMETRY IN TUMOR-BEARING NUDE-MICE

Citation
S. Kinuya et al., RHENIUM-186-MERCAPTOACETYLTRIGLYCINE-LABELED MONOCLONAL-ANTIBODY FOR RADIOIMMUNOTHERAPY - IN-VITRO ASSESSMENT, IN-VIVO KINETICS AND DOSIMETRY IN TUMOR-BEARING NUDE-MICE, Japanese journal of cancer research, 89(8), 1998, pp. 870-878
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
ISSN journal
0910-5050
Volume
89
Issue
8
Year of publication
1998
Pages
870 - 878
Database
ISI
SICI code
0910-5050(1998)89:8<870:RMFR>2.0.ZU;2-K
Abstract
Stability and immunoreactivity of Re-186-labeled monoclonal antibody w ere examined, and its in vivo kinetics was investigated in tumor-beari ng Balb/c nu/nu female mice to assess the feasibility of using it in r adioimmunotherapy (RIT), A murine IgG(1), A7, against a 45 kD glycopro tein in human colon cancer was radiolabeled with Re-186 by using a che lating method with a mercaptoacetyltriglycine (MAG3). Re-186-MAG3 comp lex was conjugated to A7 after esterification of Re-186-MAG3 with tetr afluorophenol (TFP), The efficiency of Re-186-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively, Im munoreactivity of purified Re-186-MAG3-A7 was 68.2% at infinite antige n excess, In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from Re-186-MAG3-A7 as a small mol ecular weight moiety because of autoradiolysis. The addition of ascorb ic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C cou ld effectively prevent the radiolysis of Re-186-MAG3-A7 for 7 days, Im munoreactivity of Re-186-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after th e preparation, In colon cancer xenografted mice, 31.0% of the injected dose/g of Re-186-MAG3-A7 had accumulated in the tumors at 24 h postin jection, Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body rad iation dose. These in vivo characteristics mere superior to those of A 7 labeled with radioiodine, affording greater therapeutic ratios than I-131-A7, Because of the better image quality of Re-186-MAG3-A7 as wel l as more favorable dosimetry, Re-186-MAG3-A7 would be a better choice for RIT of colon cancer than I-131-A7. These results indicated the fe asibility of RIT with Re-186-MAG3-A7, though the prevention of radioly sis of the labeled antibody should be considered.