In-line radiolabeling: a novel continuous-flow system for commercial-scale protein labeling.
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 (131)I during a single 30-min reaction run.


CONCLUSIONS
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.
Harris
Debra A
DA
Research and Development, Peregrine Pharmaceuticals Inc., Tustin, California 92780, USA.
Pellikka
Raimo
R
Gasser
Olga
O
Blaeuenstein
Peter
P
Waibel
Robert
R
Schubiger
P August
PA
King
Steven W
SW
Parseghian
Missag H
MH
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D003132:Commerce; D004339:Drug Compounding / Q000379:methods*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D017022:Flow Injection Analysis / Q000295:instrumentation*; D007553:Isotope Labeling / Q000295:instrumentation*; D009862:Online Systems; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D019275:Radiopharmaceuticals