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The Effect of Chelating Agents on the Distribution of Monoclonal Antibodies in Mice

Royal Marsden Hospital
Ludwig Institute for Cancer Research, Sutton, Surrey, UK

Correspondence: For reprints contact: K. R. Roberts, MD, Dept. of Nuclear Medicine, Royal Marsden Hospital, Downs Rd., Sutton, Surrey, UK.

ABSTRACT

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.