Rapid and efficient production of radiolabeled antibody conjugates using vacuum diafiltration guided by mathematical modeling.

Bioconjugate Chemistry
Derek W BartlettAndrew A Raubitschek

Abstract

Increasing interest in the use of radiolabeled antibodies for cancer imaging and therapy drives the need for more efficient production of the antibody conjugates. Here, we illustrate a method for rapid and efficient production of radiolabeled antibody conjugates using vacuum diafiltration guided by mathematical modeling. We apply this technique to the production of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated antibodies at the milligram and gram production scale and achieve radiolabeling efficiencies >95% using In-111. Using vacuum diafiltration, antibody-chelate conjugation and purification can be accomplished within the same vessel, and the entire process can be completed in <24 h. Vacuum diafiltration also offers safer and gentler processing conditions by eliminating the need to keep the retentate vessel under positive pressure through applied gas pressure or shear-inducing restriction points in the retentate flow path. Experimental data and mathematical model calculations suggest there exists a weak binding affinity (approximately 10(4)M(-1)) between the charged chelate molecules (e.g., DOTA) and the antibodies that slows the removal of excess chelate during purification. By analyzing the radio...Continue Reading

References

Jun 11, 1999·Nuclear Medicine and Biology·C WuM W Brechbiel
Jun 24, 2004·Biotechnology and Bioengineering·Jiahui Shao, Andrew L Zydney
Jul 29, 2004·Biotechnology and Bioengineering·Jiahui Shao, Andrew L Zydney
Jun 27, 2007·Seminars in Radiation Oncology·Roger M Macklis
Sep 1, 1948·Journal of the American Chemical Society·I M KLOTZF M WALKER

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