A transition metal complex (Venus flytrap cluster) for radioimmunodetection and radioimmunotherapy.
A novel transition metal complex, Venus flytrap cluster (VFC), is described for the preparation of radio-labeled antibodies. VFC contained 57Co, which was held tightly between the faces of two covalently bridged carborane ligands by cluster bonding of the metal with appropriate ligand orbitals. Anti-carcinoembryonic antigen monoclonal antibody T84.66 was conjugated to 57Co-VFC with full retention of immunological activity. Biodistribution studies in nude mice bearing carcinoembryonic antigen-producing tumors showed excellent tumor localization of 57Co-VFC-T84.66. The accumulation of radionuclide in normal liver was low and independent of dose, which may reflect the stability of the radionuclide complex. These results presage the use of VFC systems for binding transition metals that are clinically useful for radioimmunodiagnosis and radioimmunotherapy.
Paxton
R J
RJ
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
Beatty
B G
BG
Hawthorne
M F
MF
Varadarajan
A
A
Williams
L E
LE
Curtis
F L
FL
Knobler
C B
CB
Beatty
J D
JD
Shively
J E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D007167:Immunotherapy; D008024:Ligands; D008670:Metals; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D011863:Radioimmunoassay / Q000379:methods; D011868:Radioisotopes; D011877:Radionuclide Imaging / Q000379:methods
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D003432:Cross-Linking Reagents; D008024:Ligands; D008670:Metals; D011868:Radioisotopes