title: "Click Chip" Conjugation of Bifunctional Chelators to Biomolecules.
abstract: There is a growing demand for diagnostic procedures including in vivo tumor imaging. Radiometal-based imaging agents are advantageous for tumor imaging because radiometals (i) have a wide range of half-lives and (ii) are easily incorporated into imaging probes via a mild, rapid chelation event with a bifunctional chelator (BFC). Microfluidic platforms hold promise for synthesis of radiotracers because they can easily handle minute volumes, reduce consumption of expensive reagents, and minimize personnel exposure to radioactive compounds. Here we demonstrate the use of a "click chip" with an immobilized Cu(I) catalyst to facilitate the "click chemistry" conjugation of BFCs to biomolecules (BMs); a key step in the synthesis of radiometal-based imaging probes. The "click chip" was used to synthesize three different BM-BFC conjugates with minimal amounts of copper present in reaction solutions (∼20 ppm), which reduces or obviates the need for a copper removal step. These initial results are promising for future endeavors of synthesizing radiometal-based imaging agents completely on chip.
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Whittenberg
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine , 510 South Kingshighway Boulevard, Campus Box 8225, St. Louis, Missouri 63110, United States.
authors.forename: Hairong
authors.initials: H
authors.lastname: Li
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine , 510 South Kingshighway Boulevard, Campus Box 8225, St. Louis, Missouri 63110, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Jan
authors.initials: J
authors.lastname: Koziol
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Desai
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine , 510 South Kingshighway Boulevard, Campus Box 8225, St. Louis, Missouri 63110, United States.
authors.forename: David E
authors.identifier: 0000-0003-3432-8998
authors.initials: DE
authors.lastname: Reichert
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Paul J A
authors.identifier: 0000-0001-7348-0381
authors.initials: PJA
authors.lastname: Kenis
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D002614:Chelating Agents / Q000737:chemistry*; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry*; D061565:Cycloaddition Reaction / Q000379:methods*; D004867:Equipment Design; D056656:Lab-On-A-Chip Devices; D057054:Molecular Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000480:Alkynes; D001386:Azides; D002614:Chelating Agents; D019275:Radiopharmaceuticals; D003300:Copper