Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies.
Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers.
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Y
Y
Katoh
K
K
Nakata
K
K
Kohno
M
M
Shima
A
A
Satoh
Y
Y
Kusumoto
N
N
Ishii
T
T
Kohji
H
H
Shiku
S
S
Nagataki
D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D006801:Humans; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015689:Oncogene Protein p21(ras) / Q000276:immunology*; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D015689:Oncogene Protein p21(ras)