Radiosynthesis and ‘click’ conjugation of ethynyl‐4‐[18F]fluorobenzene — an improved [18F]synthon for indirect radiolabeling |
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| Authors: | Maxine P. Roberts Tien Q. Pham Cathy D. Jiang Trevor W. Hambley Ivan Greguric Benjamin H. Fraser |
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| Affiliation: | 1. LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), DC, NSW, Australia;2. School of Chemistry, The University of Sydney, Sydney, NSW, Australia |
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| 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. |
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| Keywords: | [18F]Fluorine click chemistry radiochemistry [18F]synthons matrix metalloproteinase inhibitors (MMPIs) positron emission tomography (PET) |
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