The effect of chelating agents on the distribution of monoclonal antibodies in mice.
The potential for altering the biodistribution of radiolabel from gallium- and indium-labeled mouse monoclonal antibodies was investigated in mice using metal chelating agents. The chelating agents used were desferrioxamine (DFO), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-di (O-hydroxyphenylacetic acid) (EDHPA), and 2,2' dipyridyl (DIPY). The mouse monoclonal antibody LICR-LON-M8 was labeled with 111In after conjugation to DTPA, and with 67Ga after conjugation to DFO. All the chelating agents except DIPY altered the biodistribution of [67Ga]citrate and [111In]citrate but did not affect the 48-hr tissue uptake of label from [111In]DTPA-M8 or [67Ga]DFO-M8, confirming the in vivo stability of the antibody conjugates. Label fixed in the tissues was inaccessible to the chelating agents, indicating that they will not be suitable for reducing the high background liver radioactivity in patients undergoing scanning with indium-labeled antibodies.
Ward
M C
MC
Roberts
K R
KR
Westwood
J H
JH
Coombes
R C
RC
McCready
V R
VR
D015082:2,2'-Dipyridyl; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D002614:Chelating Agents; D003676:Deferoxamine; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D006801:Humans; D007204:Indium; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D007204:Indium; C011813:ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid); C020758:indium trichloride; D015082:2,2'-Dipyridyl; D004369:Pentetic Acid; D003676:Deferoxamine