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First published online June 12, 2009, 10.2967/jnumed.108.056812
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Journal of Nuclear Medicine Vol. 50 No. 7 1178-1186
© 2009 by Society of Nuclear Medicine

doi: 10.2967/jnumed.108.056812

Basic Science Investigation

In-Line Radiolabeling: A Novel Continuous-Flow System for Commercial-Scale Protein Labeling

Debra A. Harris1, Raimo Pellikka2, Olga Gasser2, Peter Blaeuenstein2, Robert Waibel2, P. August Schubiger2,3, Steven W. King1 and Missag H. Parseghian1

1 Research and Development, Peregrine Pharmaceuticals Inc., Tustin, California; 2 Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen, Switzerland; and 3 Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland

Correspondence: For correspondence or reprints contact: Missag H. Parseghian, Research and Development, Peregrine Pharmaceuticals Inc., 14272 Franklin Ave., Tustin, CA 92780. E-mail: mparseghian{at}peregrineinc.com

A key limitation in developing radiotherapeutic proteins is the expense of manufacturing the drug in small batches using traditional reaction vessels. Removing limitations on the quantity of protein labeled at any one time significantly decreases the cost of production, and nowhere is the need for cost-effective radiotherapeutics more acute than in the treatment of cancer. Methods: We describe a novel method that can rapidly radiolabel, theoretically, unlimited amounts of protein, without causing significant damage to binding potency or structural integrity. Our process controls the reaction rate for the isotope and reactants as they simultaneously flow through a reaction tube. Results: We have demonstrated proof of principle by labeling nearly a gram of antibody with 481 GBq (13 Ci) of 131I during a single 30-min reaction run. Conclusion: Simple to construct, our system is already used to manufacture a radiolabeled antibody, both in the United States and in India, as part of clinical trials to treat glioblastoma multiforme. Modified, this system may be also applicable for nonradioactive labeling.

Key Words: radiolabeling • protein labeling • nuclear medicine • radiotherapeutic antibodies • glioblastoma multiforme

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.


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