Improving the tumor retention of radioiodinated antibody : aryl carbohydrate adducts

Improved methods for attaching radioiodine to monoclonal antibodies have been developed. Ten aryl carbohydrate adducts were synthesized by the reductive amination of a carbohydrate with an aryl amine, using sodium cyanoborohydride as a reducing agent. After purification by chromatography and charact...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1990-02, Vol.50 (3), p.783s-788s
Main Authors: ALI, S. A, WARREN, S. D, RICHTER, K. Y, BADGER, C. C, EARY, J. F, PRESS, O. W, KROHN, K. A, BERNSTEIN, I. D, NELP, W. B
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
Biological and medical sciences
Carbohydrates
Cellobiose
Investigative techniques, diagnostic techniques (general aspects)
Iodine Radioisotopes
Isotope Labeling
Medical sciences
Mice
Miscellaneous. Technology
Neoplasms, Experimental - metabolism
Radionuclide investigations
Tissue Distribution
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Summary:Improved methods for attaching radioiodine to monoclonal antibodies have been developed. Ten aryl carbohydrate adducts were synthesized by the reductive amination 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.
ISSN:0008-5472
1538-7445