Whittenberg Joseph J, Li Hairong, Zhou Haiying, Koziol Jan, Desai Amit V, Reichert David E, Kenis Paul J A
Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
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.
Bioconjug Chem. 2017 Apr 19;28(4):986-994. doi: 10.1021/acs.bioconjchem.6b00703. Epub 2017 Feb 9.
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.
对包括体内肿瘤成像在内的诊断程序的需求日益增长。基于放射性金属的成像剂在肿瘤成像方面具有优势，因为放射性金属（i）具有广泛的半衰期，并且（ii）通过与双功能螯合剂（BFC）的温和、快速螯合反应很容易掺入成像探针中。微流控平台有望用于放射性示踪剂的合成，因为它们可以轻松处理微量体积，减少昂贵试剂的消耗，并将人员接触放射性化合物的风险降至最低。在这里，我们展示了使用带有固定化Cu（I）催化剂的“点击芯片”来促进BFC与生物分子（BM）的“点击化学”共轭；这是基于放射性金属的成像探针合成中的关键步骤。“点击芯片”用于合成三种不同的BM-BFC共轭物，反应溶液中铜的含量极少（约20 ppm），这减少或消除了去除铜步骤的必要性。这些初步结果为未来完全在芯片上合成基于放射性金属的成像剂的努力带来了希望。
