Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice

Abstract

Our previous studies with a ⁹⁰Y‐labelled antibody against carcinoembryonic antigen (CEA) conjugated to the cyclic anhydride‐DTPA (CA‐DTPA) indicated that the accretion of ⁹⁰Y in the bone may limit the application of ⁹⁰Y‐labelled antibodies for therapy. In this report, we have compared the tumor targeting of CA‐DTPA‐conjugated antibody to antibody conjugated with 4 isothiocyanatobenzyl (ITC‐Bz) derivatives of DTPA in nude mice bearing a human colonic tumor xenograft. In biodistribution studies using an ¹¹¹In‐labelled anti‐CEA murine monoclonal antibody (MAb), the CA‐DTPA‐conjugated MAb showed lower tumor uptake, faster blood clearance, and higher accretion in the liver than any of the 4 ITC‐Bz‐DTPA‐conjugated MAbs. There were smaller differences among the 4 ITC‐Bz‐DTPA conjugates. Whole‐body autoradiography of animals given ⁹⁰Y‐MAb prepared with the CA‐DTPA or the ITC‐Bz‐DTPA showed less radioactivity in the bone with the ITC‐Bz‐DTPA‐MAb than the CA‐DTPA‐MAb. ⁹⁰Y uptake in the bone corresponded with regions of low proliferative activity as defined by ³H‐labelled thymidine, suggesting that the ⁹⁰Y was in the cortex rather than the marrow. These studies clearly show an advantage of the ITC‐Bz‐DTPA derivatives for ⁹⁰Y and ¹¹¹In labelling of MAbs.