Selection of a DTPA chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice
| Autor: | Robert M. Sharkey, Cecilia Motta-Hennessy, David M. Goldenberg, Otto A. Gansow, Martin W. Brechbiel, Irwin Fand, Anastasia L. Jones, Gary L. Griffiths |
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| Rok vydání: | 1990 |
| Předmět: |
Cancer Research
Biodistribution Pathology medicine.medical_specialty medicine.drug_class Ratón animal diseases Mice Nude Monoclonal antibody Whole-Body Counting chemistry.chemical_compound Mice Carcinoembryonic antigen Labelling medicine Animals Tissue Distribution Yttrium Radioisotopes Chelating Agents biology Chemistry organic chemicals Immunotoxins Indium Radioisotopes Antibodies Monoclonal respiratory system Pentetic Acid Molecular biology Carcinoembryonic Antigen Oncology Colonic Neoplasms cardiovascular system biology.protein Autoradiography Female Antibody Thymidine Neoplasm Transplantation circulatory and respiratory physiology Conjugate |
| Zdroj: | International journal of cancer. 46(1) |
| ISSN: | 0020-7136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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