Radiosynthesis and "click' conjugation of ethynyl-4-[18F]fluorobenzene an improved [18F]synthon for indirect radiolabeling

Reproducible methods for [F-18]radiolabeling of biological vectors are essential for the development of new [F-18]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 [F-18]radiolabeling of such molecules, our group has synthesized ethynyl-4-[F-18]fluorobenzene ([F-18]2, [F-18]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 [F-18]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first proof of principle' conjugation of [F-18]2 to 1-azido-1-deoxy--d-glucopyranoside (3) gave the desired radiolabeled product [F-18]4 in excellent radiochemical yield (76 +/- 4% ndc RCY (11% overall)). As a second example, the conjugation of [F-18]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [F-18]6 in very good radiochemical yield (56 +/- 12% ndc RCY (8% overall)). Total preparation time for [F-18]4 and [F-18]6 including [F-18]F- drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70min. The radiochemical purity of synthon [F-18]2 and the conjugated products, [F-18]4 and [F-18]6, were all greater than 98%. The specific activities of [F-18]2 and [F-18]6 were low, 5.97 and 0.17MBqnmol(-1), respectively.