Effect of DTPA conjugation on the antigen binding activity and biodistribution of monoclonal antibodies against alpha-fetoprotein.
Indium-111-(111In) labeled monoclonal antibodies (Ab) prepared with a bifunctional chelating agent, diethylenetriaminepentaacetic acid (DTPA), have been used for the radioimmunoimaging of cancer. In the present experiment, using monoclonal Ab against human alpha-fetoprotein (AFP) as a model, we have studied the effect of DTPA conjugation on the antigen binding activity and the biodistribution in nude mice transplanted with AFP-producing human testicular tumor. In Ab heavily conjugated with DTPA, the Scatchard plot analysis demonstrated that the maximum binding capacity rather than the affinity constant was affected. Under selected conditions, 111In-labeled Ab were made available with almost full retention of the antigen binding activity and scintigrams of nude mice clearly delineated the site of the tumor. However, the number of DTPA molecules incorporated per Ab molecule markedly influenced the in vivo biodistribution as well as the in vitro antigen binding activity.
Sakahara
H
H
Endo
K
K
Nakashima
T
T
Koizumi
M
M
Ohta
H
H
Torizuka
K
K
Furukawa
T
T
Ohmomo
Y
Y
Yokoyama
A
A
Okada
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D007204:Indium; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000378:metabolism; D011868:Radioisotopes; D011877:Radionuclide Imaging; D013724:Teratoma / Q000000981:diagnostic imaging* / Q000473:pathology; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D000509:alpha-Fetoproteins; D007204:Indium; D004369:Pentetic Acid