Research Article
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Published Online: 29 January 2009

Improved Tumor Localization and Radioimaging with Chemically Modified Monoclonal Antibodies

Publication: Cancer Biotherapy & Radiopharmaceuticals
Volume 11, Issue Number 3

Abstract

A method for the chemical modification of monoclonal antibodies using the heterobifunctional crosslinker succinimidyl 3-(2-pyridyldithio)propionate (SPDP), has been developed which dramatically alters the physiochemical properties of antibody reagents. For these studies, three murine monoclonal antibodies, B72.3, Lym-1, and TNT-1 were used to demonstrate the effects of chemical modification on clearance and biodistribution in tumor-bearing nude mice. In vitro, all three antibodies, modified to the same degree with SPDP, showed equal immunoreactivities and lower non-specific binding. Modified antibodies also were found to have lower isoelectric points compared to unmodified controls. In vivo, modified antibodies unexpectedly were found to have 2-6 times faster clearance in tumor-bearing nude mice similar to rates obtained with their F(ab′)2 fragments. Paired-label in vivo biodistribution and external imaging experiments with intact antibodies and F(ab′)2 fragments demonstrated that chemically modified antibodies gave 1.5-3 fold higher tumor uptake and retained less activity in normal organs thus markedly increasing the tumor to normal organ ratios. Because of these results, chemically modified antibodies produced clearer images at earlier time points by external scintigraphy. As "stealth " molecules, chemically modified monoclonal antibodies appear to have significantly improved uptake in tumors and faster clearance times compared to native molecules. These results suggest that alteration of the physicochemical properties of monoclonal antibodies may generate improved reagents for in vivo use.

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cover image Cancer Biotherapy and Radiopharmaceuticals
Cancer Biotherapy & Radiopharmaceuticals
Volume 11Issue Number 3June 1996
Pages: 203 - 215
PubMed: 10851539

History

Published online: 29 January 2009
Published in print: June 1996

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