1] Division of Nuclear Medicine and Molecular Imaging, Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA [2].
Division of Nuclear Medicine and Molecular Imaging, Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Nat Commun. 2014 Jul 9;5:4365. doi: 10.1038/ncomms5365.
Fluorine-18 (t½=109.7 min) is the most commonly used isotope to prepare radiopharmaceuticals for molecular imaging by positron emission tomography (PET). Nucleophilic aromatic substitution reactions of suitably activated (electron-deficient) aromatic substrates with no-carrier-added [(18)F]fluoride ion are routinely carried out in the synthesis of radiotracers in high specific activities. Despite extensive efforts to develop a general (18)F-labelling technique for non-activated arenes there is an urgent and unmet need to achieve this goal. Here we describe an effective solution that relies on the chemistry of spirocyclic hypervalent iodine(III) complexes, which serve as precursors for rapid, one-step regioselective radiofluorination with [(18)F]fluoride. This methodology proves to be efficient for radiolabelling a diverse range of non-activated functionalized arenes and heteroarenes, including arene substrates bearing electron-donating groups, bulky ortho functionalities, benzylic substituents and meta-substituted electron-withdrawing groups. Polyfunctional molecules and a range of previously elusive (18)F-labelled building blocks, compounds and radiopharmaceuticals are synthesized.
氟-18（t1/2=109.7 分钟）是最常用于通过正电子发射断层扫描（PET）制备放射性药物的同位素。在高比活度放射性示踪剂的合成中，通常通过适当活化（缺电子）芳基底物的亲核芳香取代反应与无载体添加的[（18）F]氟离子进行。尽管已经做出了广泛的努力来开发用于非活化芳烃的通用（18）F 标记技术，但实现这一目标仍然是迫切需要的。在这里，我们描述了一种有效的解决方案，该方案依赖于螺环高碘（III）配合物的化学，这些配合物可用作[（18）F]氟化物快速一步区域选择性放射性氟化的前体。该方法被证明对多种非活化官能化芳烃和杂芳烃的放射性标记有效，包括带有供电子基团、大邻位官能团、苄基取代基和间位取代吸电子基团的芳基底物。多官能分子和一系列以前难以获得的（18）F 标记的构建块、化合物和放射性药物被合成。
