Premium
Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice
Author(s) -
Sharkey Robert M.,
MottaHennessy Cecilia,
Gansow Otto A.,
Brechbiel Martin W.,
Fand Irwin,
Griffiths Gary L.,
Jones Anastasia L.,
Goldenberg David M.
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910460116
Subject(s) - monoclonal antibody , biodistribution , conjugate , chemistry , antibody , carcinoembryonic antigen , microbiology and biotechnology , conjugated system , radioimmunotherapy , in vitro , medicine , biochemistry , biology , immunology , cancer , mathematical analysis , mathematics , organic chemistry , polymer
Our previous studies with a 90 Y‐labelled antibody against carcinoembryonic antigen (CEA) conjugated to the cyclic anhydride‐DTPA (CA‐DTPA) indicated that the accretion of 90 Y in the bone may limit the application of 90 Y‐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 111 In‐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 90 Y‐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. 90 Y uptake in the bone corresponded with regions of low proliferative activity as defined by 3 H‐labelled thymidine, suggesting that the 90 Y was in the cortex rather than the marrow. These studies clearly show an advantage of the ITC‐Bz‐DTPA derivatives for 90 Y and 111 In labelling of MAbs.