title: In-line radiolabeling: a novel continuous-flow system for commercial-scale protein labeling.
abstract: 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.
authors.affiliation: Research and Development, Peregrine Pharmaceuticals Inc., Tustin, California 92780, USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Harris
authors.forename: Raimo
authors.initials: R
authors.lastname: Pellikka
authors.forename: Olga
authors.initials: O
authors.lastname: Gasser
authors.forename: Peter
authors.initials: P
authors.lastname: Blaeuenstein
authors.forename: Robert
authors.initials: R
authors.lastname: Waibel
authors.forename: P August
authors.initials: PA
authors.lastname: Schubiger
authors.forename: Steven W
authors.initials: SW
authors.lastname: King
authors.forename: Missag H
authors.initials: MH
authors.lastname: Parseghian
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D019275:Radiopharmaceuticals