Improving the tumor retention of radioiodinated antibody: Aryl carbohydrate adducts

Seham A. Ali, Stephen D. Warren, Karen Y. Richter, Christopher C. Badger, Janet F. Eary, Oliver W. Press, Kenneth Krohn, Irwin D. Bernstein, Wil B. Nelp

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Abstract

Improved methods for attaching radioiodine to monoclonal antibodies have been developed. Ten aryl carbohydrate adducts were synthesized by the reductive animation of a carbohydrate with an aryl amine, using sodium cyanoborohydride as a reducing agent. After purification by chromatography and characterization by nuclear magnetic resonance they were iodinated using the chloramine-T method. Iodinated adducts were activated with cyanuric chloride and incubated with protein at room temperature. The immunoreactivity and avidity of radioiodinated tyramine cellobiose (TCB) labeled antibody were fully preserved when compared to electrophilically radioiodinated antibody. Radioiodinated TCB-and tyramine glucose-labeled monoclonal antibodies showed much greater intracellular retention of radioiodine when compared to electrophilically radioiodinated monoclonal antibodies. Neither radioiodinated tyramine nor radioiodinated TCB had any specific tissue uptake or retention. In mice the retention of radioiodinated TCB labeled anti-Thy-1.1 antibody (1A14) by Thy-1.1-bearing lymphoma cells was 2 times greater than that of chloramine-T labeled 1A14 antibody, whereas the plasma clearance curve and uptake in normal tissues was not changed. This method of radioiodinating monoclonal antibodies increases the retention time of radioiodine in tumor and thus may obviate the problem of intracellular deiodination, a perceived disadvantage of electrophilically iodinated antibodies, with respect to tumor retention of radioactivity.

Original languageEnglish (US)
JournalCancer Research
Volume50
Issue number3 SUPPL.
Publication statusPublished - 1990
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ali, S. A., Warren, S. D., Richter, K. Y., Badger, C. C., Eary, J. F., Press, O. W., ... Nelp, W. B. (1990). Improving the tumor retention of radioiodinated antibody: Aryl carbohydrate adducts. Cancer Research, 50(3 SUPPL.).