title: Radiosynthesis and 'click' conjugation of ethynyl-4-[(18)F]fluorobenzene--an improved [(18)F]synthon for indirect radiolabeling.
abstract: Reproducible methods for [(18)F]radiolabeling of biological vectors are essential for the development of new [(18)F]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 [(18)F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[(18)F]fluorobenzene ([(18)F]2, [(18)F]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 [(18)F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first 'proof of principle' conjugation of [(18)F]2 to 1-azido-1-deoxy-β-D-glucopyranoside (3) gave the desired radiolabeled product [(18)F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [(18)F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [(18)F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [(18)F]4 and [(18)F]6 including [(18)F]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 [(18)F]2 and the conjugated products, [(18)F]4 and [(18)F]6, were all greater than 98%. The specific activities of [(18)F]2 and [(18)F]6 were low, 5.97 and 0.17 MBq nmol(-1), respectively.
authors.affiliation: LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee, DC, NSW, 2232, Australia.
authors.forename: Maxine P
authors.initials: MP
authors.lastname: Roberts
authors.affiliation: LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee, DC, NSW, 2232, Australia.
authors.forename: Tien Q
authors.initials: TQ
authors.lastname: Pham
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Doan
authors.affiliation: LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee, DC, NSW, 2232, Australia.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Jiang
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Hambley
authors.affiliation: LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee, DC, NSW, 2232, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.affiliation: LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee, DC, NSW, 2232, Australia.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Fraser
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D057930:Click Chemistry / Q000379:methods; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D019275:Radiopharmaceuticals; C000610674:ethynyl-4-fluorobenzene; D000114:Acetylene
keywords: [18F]Fluorine; [18F]synthons; click chemistry; matrix metalloproteinase inhibitors (MMPIs); positron emission tomography (PET); radiochemistry