PMID: 2491892Jan 1, 1989Paper

Synthesis of novel bifunctional chelators and their use in preparing monoclonal antibody conjugates for tumor targeting

Journal of Medicinal Chemistry
D A WesterbergD K Johnson

Abstract

Bifunctional derivatives of the chelating agents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, in which a p-isothiocyanatobenzyl moiety is attached at the methylene carbon atom of one carboxymethyl arm, was synthesized by reductive alkylation of the relevant polyamine with (p-nitrophenyl)pyruvic acid followed by carboxymethylation, reduction of the nitro group, and reaction with thiophosgene. The resulting isothiocyanate derivatives reacted with monoclonal antibody B72.3 to give antibody-chelator conjugates containing 3 mol of chelator per mole of immunoglobulin, without significant loss of immunological activity. Such conjugates, labeled with the radioisotopic metal indium-111, selectively bound a human colorectal carcinoma implanted in nude mice when given intravenously. Uptake into normal tissues was comparable to or lower than that reported for analogous conjugates with known bifunctional chelators. It is concluded that substitution with a protein reactive group at this position in polyaminopolycarboxylate chelators does not alter the chelating properties of these molecules to a sufficient extent to adversely affect biodistribution and thus provides a general method for the synthesis of such chelat...Continue Reading

Citations

Aug 1, 1992·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·R ReillyA Marks
Jul 1, 1996·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·C JolleyP J Blower
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Mar 11, 2005·Advanced Drug Delivery Reviews·Makiya NishikawaMitsuru Hashida
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Dec 20, 2007·Organic Letters·Jongdoo Lim, Eric E Simanek

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