PMID: 2114375Jul 15, 1990Paper

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

International Journal of Cancer. Journal International Du Cancer
R M SharkeyD M Goldenberg

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 lab...Continue Reading

References

Jul 25, 1977·Biochemical and Biophysical Research Communications·G E Krejcarek, K L Tucker
Jan 1, 1987·Journal of Cancer Research and Clinical Oncology·D M Goldenberg
Nov 1, 1966·Transplantation·D M GoldenbergK Elster
May 6, 1983·Science·D J HnatowichP W Doherty
Jan 1, 1957·Advances in Biological and Medical Physics·W F BALE, I L SPAR

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Citations

Jan 1, 1991·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·C Motta-HennessyD M Goldenberg
Aug 1, 1992·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·R ReillyA Marks
Jan 8, 2009·Bioconjugate Chemistry·Tapan K Nayak, Martin W Brechbiel
May 5, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Sibaprasad Bhattacharyya, Manish Dixit
Sep 25, 2003·Cancer Biotherapy & Radiopharmaceuticals·Asa Liljegren SundbergVladimir Tolmachev
Mar 2, 2010·Cancer Biotherapy & Radiopharmaceuticals·Robert M SharkeyDavid M Goldenberg
Apr 9, 2009·PMC Biophysics·Balázs Szalontai
May 25, 2004·Leukemia & Lymphoma·Angelika Bischof Delaloye
May 8, 1992·International Journal of Cancer. Journal International Du Cancer·R M SharkeyD M Goldenberg

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