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-[18 F]fluoro-m-hydroxyphenethylguanidine ([18 F]4F-MHPG) and 3-[18 F]fluoro-p-hydroxyphenethylguanidine ([18 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 Patlak graphical analysis. 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 [18 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 three-fold higher than those achieved previously using an iodonium salt precursor. With further optimization and scale-up, this approach could potentially support commercial distribution of [18 F]4F-MHPG to PET centers without on-site radiochemistry facilities.

中文翻译：

---

使用碘鎓叶立德前体改进 4-[18 F] 氟-间-羟基苯乙基胍的合成

我们实验室最近开发了氟 18 标记的羟基苯乙基胍，作为一类新的 PET 放射性药物，用于量化心脏病患者的局部心脏交感神经密度。4-[18 F] 氟-间-羟基苯乙基胍 ([18 F]4F-MHPG) 和 3-[18 F] 氟-对-羟基苯乙基胍 ([18 F]3F-PHPG) 在人类受试者中的研究表明，这些放射性示踪剂可用于使用 Patlak 图形分析生成区域交感神经密度的高分辨率图。以前，这些化合物是使用碘盐前体合成的，为现场临床 PET 研究提供了足够的放射化学产率。然而，我们有兴趣探索可以提供显着更高放射化学产率的新方法。螺环碘鎓叶立德前体最近被确定为富电子芳族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多种优势。本研究的目的是制备用于合成 [18 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功效。在优化的自动反应条件下，碘鎓叶立德前体提供的放射化学产率平均为 7.8 ± 1.4%（n = 8，EOS，未衰减校正），比以前使用碘鎓盐前体获得的产率高出约三倍。随着进一步优化和扩大，这种方法有可能支持 [18 F]4F-MHPG 向 PET 中心的商业分销，而无需现场放射化学设施。