Radiosynthesis and ‘click’ conjugation of ethynyl‐4‐[18F]fluorobenzene — an improved [18F]synthon for indirect radiolabeling
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Date
2015-11-03
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John Wiley and Sons
Abstract
Reproducible methods for [18F]radiolabeling of biological vectors are essential for the development of new [18F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi-step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [18F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[18F]fluorobenzene ([18F]2, [18F]EYFB) in a single step (14 ± 2% non-decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne-functionalized synthon [18F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first ‘proof of principle’ conjugation of [18F]2 to 1-azido-1-deoxy-β-d-glucopyranoside (3) gave the desired radiolabeled product [18F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [18F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [18F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [18F]4 and [18F]6 including [18F]F− drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [18F]2 and the conjugated products, [18F]4 and [18F]6, were all greater than 98%. The specific activities of [18F]2 and [18F]6 were low, 5.97 and 0.17 MBq nmol−1, respectively. © 2015 John Wiley & Sons, Ltd.
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Keywords
Fluorine 18, Radiopharmaceuticals, Molecules, Positron computed tomography, High-performance liquid chromatography, Synthesis, Radiochemistry
Citation
Roberts, M. P., Pham, T. Q., Doan, J., Jiang, C. D., Hambley, T. W., Greguric, I., & Fraser, B. H. (2015). Radiosynthesis and ‘click’conjugation of ethynyl‐4‐[18F] fluorobenzene—an improved [18F] synthon for indirect radiolabeling. Journal of Labelled Compounds and Radiopharmaceuticals, 58(13-14), 473-478. doi:10.1002/jlcr.3354