Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice.
Stability and immunoreactivity of 186Re-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 IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-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 degrees C could effectively prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re-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 186Re-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 131I-A7. Because of the better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re-MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These results indicated the feasibility of RIT with 186Re-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.
Department of Nuclear Medicine, Kanazawa University School of Medicine.
S
S
Kinuya
K
K
Yokoyama
H
H
Tega
T
T
Hiramatsu
S
S
Konishi
W
W
Yamamoto
N
N
Shuke
T
T
Aburano
N
N
Watanabe
T
T
Takayama
T
T
Michigishi
N
N
Tonami
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D011829:Radiation Dosage; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009842:Oligopeptides; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C114893:rhenium-mercaptoacetyltriglycine; D012211:Rhenium