In-line radiolabeling: a novel continuous-flow system for commercial-scale protein labeling

J Nucl Med. 2009 Jul;50(7):1178-86. doi: 10.2967/jnumed.108.056812. Epub 2009 Jun 12.

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.

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.

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Commerce
  • Drug Compounding / methods*
  • Equipment Design
  • Equipment Failure Analysis
  • Flow Injection Analysis / instrumentation*
  • Isotope Labeling / instrumentation*
  • Online Systems
  • Radioisotopes / chemistry*
  • Radiopharmaceuticals / chemistry*

Substances

  • Antibodies, Monoclonal
  • Radioisotopes
  • Radiopharmaceuticals