“Click Chip” Conjugation of Bifunctional Chelators to Biomolecules

• Published in: Bioconjugate chemistry 2017-04, Vol.28 (4), p.986-994
• Main Authors: Whittenberg, Joseph J, Li, Hairong, Zhou, Haiying, Koziol, Jan, Desai, Amit V, Reichert, David E, Kenis, Paul J. A
• Format: Article
• Language: English
• Subjects: Alkynes - chemistry; Azides - chemistry; Biochemistry; Biomolecules; Catalysis; Chelating agents; Chelating Agents - chemistry; Chelation; Chemical synthesis; Click Chemistry - methods; Conjugation; Copper; Copper - chemistry; Cycloaddition Reaction - methods; Equipment Design; Imaging; Lab-On-A-Chip Devices; Microfluidics; Molecular Imaging; Molecules; Probes; Radioactive tracers; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Reagents; Tumors
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.6b00703

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.