In vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labeled with indium-111.
Monoclonal antibody 2G3 directed against a high molecular weight glycoprotein on breast and ovarian cancer cells was conjugated with bicyclic DTPA (or EDTA) anhydride or benzyl isothiocyanate DTPA (benzyl DTPA) and labeled with 111In. DTPA anhydride was more reactive with the antibody than benzyl DTPA, and kinetics of labeling with 111In were more rapid for DTPA substituted 2G3 than for benzyl DTPA substituted 2G3. On the other hand, 111In-2G3 conjugates prepared using DTPA anhydride were subject to more extensive dimerization and higher losses in immunoreactivity than those prepared using benzyl DTPA. On the basis of measurement of transchelation to transferrin, the stability of 111In-2G3 prepared using DTPA anhydride or benzyl DTPA did not differ during incubation in human plasma for 6 days at 37 degrees C. These results suggest that an important advantage of benzyl DTPA over DTPA anhydride for preparing 111In-labeled antibodies is the prevention of intermolecular (and intramolecular) crosslinking during conjugation which ultimately leads to alterations in conformation and losses in immunoreactivity of the radioimmunoconjugate.
Reilly
R
R
Division of Nuclear Medicine, Toronto Hospital, Canada.
Lee
N
N
Houle
S
S
Law
J
J
Marks
A
A
D000911:Antibodies, Monoclonal; D001202:Ascitic Fluid; D004355:Drug Stability; D004492:Edetic Acid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D010051:Ovarian Neoplasms / Q000097:blood; D004369:Pentetic Acid
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D004369:Pentetic Acid; D004492:Edetic Acid