Open AccessRhenium‐186‐mercaptoacetyltriglycine‐labeled Monoclonal Antibody for Radioimmunotherapy: In vitro Assessment, in vivo Kinetics and Dosimetry in Tumor‐bearing Nude Mice
Author(s) -
Kinuya Seigo,
Yokoyama Kunihiko,
Tega Harunobu,
Hiramatsu Takashi,
Konishi Shota,
Yamamoto Wakako,
Shuke Noriyuki,
Aburano Tamio,
Watanabe Naoto,
Takayama Terahiko,
Michigishi Takatoshi,
Tonami Norihisa
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00642.x
Subject(s) - radioimmunotherapy , in vivo , ascorbic acid , monoclonal antibody , chemistry , nuclear medicine , microbiology and biotechnology , medicine , antibody , radiochemistry , immunology , biology , food science
Stability and immunoreactivity of 186 Re‐labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor‐bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG 1 , A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186 Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186 Re‐MAG3 complex was conjugated to A7 after esterification of 186 Re‐MAG3 with tetrafluorophenol (TFP). The efficiency of 186 Re‐MAG3‐TFP production and the labeling efficiency of A7 were 51–59% and 57–60%, respectively. Immunoreactivity of purified 186 Re‐MAG3‐A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4°C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186 Re‐MAG3‐A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at –80°C could effectively prevent the radiolysis of 186 Re‐MAG3‐A7 for 7 days. Immunoreactivity of 186 Re‐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 the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186 Re‐MAG3‐A7 had accumulated in the tumors at 24 h postinjection. 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 radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131 I‐A7. Because of the better image quality of 186 Re‐MAG3‐A7 as well as more favorable dosimetry, 186 Re‐MAG3‐A7 would be a better choice for RIT of colon cancer than 131 I‐A7. These results indicated the feasibility of RIT with 186 Re‐MAG3‐A7, though the prevention of radiolysis of the labeled antibody should be considered.