The stability in liver homogenates of indium-111 and yttrium-90 attached to antibody via two popular chelators.

To investigate the influence of chelator on the stability in liver homogenates of 111In and 90Y-labeled antibodies, the C110 antibody was conjugated with the cyclic anhydride of DTPA (cDTPA) and with isocyanatobenzyl-DTPA (SCN-Bz-DTPA) and labeled with both radionuclides. After incubation in fresh liver homogenates at 37 degrees C for 1-2 days, the soluble fraction was analyzed by filtration, HPLC and TLC to determine the nature and extent of transchelation of the label and catabolism of the antibody. The loss of activity from antibody, as shown by passage through a low molecular weight (10 kDa cut-off) filter, was 3-5 times more pronounced for 90Y (51 and 68% at 1 and 2 days) than 111In (11 and 29%, respectively). No significant difference was observed between chelators. Furthermore, analysis of these low molecular weight species showed that even at 1 day, 90Y in contrast to 111In was present as one or more weak complexes and therefore no longer chelated to either DTPA or Bz-DTPA. Little evidence was observed for instability in liver of the thiourea bond whereby SCN-Bz-DTPA is attached to the antibody. By contrast the identification of 111In-DTPA in the homogenates demonstrates the instability of the amide bond generated by cDTPA conjugation. In conclusion, as expected, 90Y was shown to form less stable chelates than 111In, however, in this investigation the greater denticity of Bz-DTPA over DTPA did not improve stability with either radiolabel.