Microfluidic preparation of a 89Zr-Labeled trastuzumab single-patient dose

Brian D. Wright, Joseph Whittenberg, Amit Desai, Christina DiFelice, Paul J.A. Kenis, Suzanne E. Lapi, David E. Reichert

Research output: Contribution to journalArticlepeer-review


89Zr-labeled antibodies are being investigated in several clinical trials; however, the time requirement for synthesis of clinical doses can hinder patient throughput because of scheduling difficulties. Additionally, low specific activity due to poor labeling efficiency can require larger amounts of the radiopharmaceutical to be administered, possibly leading to adverse side effects. Here, we describe the design and evaluation of a microfluidic reactor capable of synthesizing a single clinical dose of 89Zr-labeled antibody. 89Zr-labeled trastuzumab was chosen for this validation because it is currently being evaluated in clinical trials for imaging human epidermal growth factor receptor 2 positive cancer patients. Methods: A microreactor fabricated from polydimethylsiloxane/glass was silanated with trimethoxy(octadecyl) silane to reduce antibody adsorption. Desferrioxamine-p-benzylisothiocyanate (DFO-Bz-NCS) was conjugated to trastuzumab in an 8:1 molar ratio following the literature procedures using aseptic techniques. Radiolabeling was performed by pumping 89Zr-oxalate and DFO-Bz-trastuzumab into the microfluidic reactor at a total rate of 20 μL/min in ratios varying from 1:37 to 1:592 mg:MBq at 37 C to achieve optimal labeling. Results: Silanated reactors showed low antibody adsorption in comparison to unmodified reactors (95% monoclonal antibody recovered vs. 0% recovered). Labeling of the modified trastuzumab was shown to be achievable at a specific activity above the reported literature value of 220 MBq/mg. A high radiochemical purity was achieved without an incubation period at specific activities of less than 148 MBq/mg; however, specific activities up to 592 MBq/mg could be achieved with an incubation period. Clinical doses were able to be prepared and passed all quality control guidelines set by the Food and Drug Administration. Samples were sterile, colorless, and radiochemically pure (100%); maintained the ability to bind to the intended receptor; formed a minimal amount of aggregates (1% 4%); and were completed within 45 60 min. Conclusion: 89Zr-labeled trastuzumab for use in a clinical setting was synthesized in a microfluidic reactor in under an hour while reducing the amount of handling required by a technician. Use of this compact platform not only could enable the use of radiolabeled antibodies to become a common practice, but also could spread the use of radiolabeled antibodies beyond locations with cyclotron facilities. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Original languageEnglish (US)
Pages (from-to)747-752
Number of pages6
JournalJournal of Nuclear Medicine
Issue number5
StatePublished - May 1 2016


  • Antibodies
  • GMP
  • Microfluidics
  • Trastuzumab
  • Zr

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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