Jung Yong-Woon, Gu Guie, Raffel David M
Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
J Labelled Comp Radiopharm. 2019 Oct;62(12):835-842. doi: 10.1002/jlcr.3791. Epub 2019 Aug 8.
Fluorine-18 labeled hydroxyphenethylguanidines were recently developed in our laboratory as a new class of PET radiopharmaceuticals for quantifying regional cardiac sympathetic nerve density in heart disease patients. Studies of 4-[ F]fluoro-m-hydroxyphenethylguanidine ([ F]4F-MHPG) and 3-[ F]fluoro-p-hydroxyphenethylguanidine ([ F]3F-PHPG) in human subjects have shown that these radiotracers can be used to generate high-resolution maps of regional sympathetic nerve density using the Patlak graphical method. Previously, these compounds were synthesized using iodonium salt precursors, which provided sufficient radiochemical yields for on-site clinical PET studies. However, we were interested in exploring new methods that could offer significantly higher radiochemical yields. Spirocyclic iodonium ylide precursors have recently been established as an attractive new approach to radiofluorination of electron-rich aromatic compounds, offering several advantages over iodonium salt precursors. The goal of this study was to prepare a spirocyclic iodonium ylide precursor for synthesizing [ F]4F-MHPG and evaluate its efficacy in production of this radiopharmaceutical. Under optimized automated reaction conditions, the iodonium ylide precursor provided radiochemical yields averaging 7.8% ± 1.4% (n = 8, EOS, not decay corrected), around threefold higher than those achieved previously using an iodonium salt precursor. With further optimization and scale-up, this approach could potentially support commercial distribution of [ F]4F-MHPG to PET centers without on-site radiochemistry facilities.
我们实验室最近开发了氟-18标记的羟基苯乙胍,作为一类新型的正电子发射断层显像(PET)放射性药物,用于定量心脏病患者的局部心脏交感神经密度。对4-[F]氟间羟基苯乙胍([F]4F-MHPG)和3-[F]氟对羟基苯乙胍([F]3F-PHPG)在人体受试者中的研究表明,这些放射性示踪剂可使用Patlak图解法生成局部交感神经密度的高分辨率图谱。此前,这些化合物是使用碘鎓盐前体合成的,其放射性化学产率足以满足现场临床PET研究的需求。然而,我们有兴趣探索能够提供显著更高放射性化学产率的新方法。螺环碘鎓叶立德前体最近已成为富电子芳香化合物放射性氟化的一种有吸引力的新方法,与碘鎓盐前体相比具有若干优势。本研究的目的是制备一种用于合成[F]4F-MHPG的螺环碘鎓叶立德前体,并评估其在生产这种放射性药物中的效能。在优化的自动化反应条件下,碘鎓叶立德前体的放射性化学产率平均为7.8%±1.4%(n = 8,EOS,未进行衰变校正),比之前使用碘鎓盐前体所达到的产率高出约三倍。通过进一步优化和扩大规模,这种方法有可能支持将[F]4F-MHPG商业配送至没有现场放射化学设施的PET中心。