422528 Microreactors with Immobilized Cu(I) for “Click Chemistry” Synthesis of Molecular Imaging Probes

Monday, November 9, 2015: 1:50 PM
355F (Salt Palace Convention Center)
Joseph Whittenberg1, Hairong Li2, Haiying Zhou2, Amit V. Desai1, Jan Koziol1, David E. Reichert2 and Paul J.A. Kenis1, (1)Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, (2)Radiological Sciences Division at Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO

Radiotracers are a type of molecular imaging probe commonly used for detecting and diagnosing cancer.  Radiotracers are typically produced in bulky automated synthesis modules that consume large quantities of expensive reagents and require large amounts of space and shielding.1,2 Microreactors can address both of these issues due to their inherently small size.  Additionally, conventional radiotracer synthesis methods involve many tedious steps, such as protection/de-protection steps to prevent unwanted side reactions with tumor-targeting biomolecules.  The advent of “click chemistry”, especially Cu(I) click chemistry, has addressed this issue and has the potential to simplify radiotracer synthesis.3  However, the Cu(I) catalyst is cytotoxic and must be removed prior to use.

Here we present a microfluidic “click chip” with an immobilized Cu(I) catalyst to synthesize radiotracer precursors by covalently bonding radiometal chelators to biomolecules.  The immobilization procedure was qualitatively verified by colorimetric changes and confirmed using X-ray photoelectron spectroscopy.  The amount of immobilized Cu(I) was quantified using a radioactive Cu-64 assay (~1100 nmol Cu)4, and catalyst loss was characterized using inductively coupled plasma mass spectrometry.  The microreactor was validated and reaction conditions optimized by bonding a chelator to a small peptide.  Two other metal chelator conjugation reactions were performed using “click chips” to verify the microreactors’ ability to synthesize different radiotracer precursors.  Reaction yields depended on the type of biomolecule and chelator used and varied from ~45%–85%.  Additionally, the click chips were stable after multiple uses (~20).  To the best of our knowledge this is the first microreactor with Cu(I) catalyst immobilized to the reactor walls, and has the potential to reduce reagent use and minimize purification requirements for radiotracer synthesis.


1.            J. M. Gillies, C. Prenant, G. N. Chimon, G. J. Smethurst, W. Perrie, I. Hambletta, B. Dekker and J. Zweit, Appl Radiat Isotopes, 2006, 64, 325-332.

2.            W. Y. Lin, Y. J. Wang, S. T. Wang and H. R. Tseng, Nano Today, 2009, 4, 470-481.

3.            C. Wangler, R. Schirrmacher, P. Bartenstein and B. Wangler, Curr. Med. Chem., 2010, 17, 1092-1116.

4.            H. Li, J. J. Whittenberg, H. Zhou, D. Ranganathan, A. V. Desai, J. Koziol, D. Zeng, P. J. A. Kenis and D. E. Reichert, RSC Advances, 2015, 5, 6142-6150.

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See more of this Session: Microreaction Engineering II
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