(4-[¹⁸F]fluoro-m-hydroxyphenethyl)guanidine | 1426298-34-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (4-[¹⁸F]fluoro-m-hydroxyphenethyl)guanidine
• 英文别名: [¹⁸F]4F-MHPG；4F-Mhpg F-18；2-[2-(4-(18F)fluoranyl-3-hydroxyphenyl)ethyl]guanidine
• CAS: 1426298-34-1
• 化学式: C₉H₁₂FN₃O
• 分子量: 196.214
• InChiKey: DBVYMDMGVRXUPK-LMANFOLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-benzyloxy-4-N,N-dimethylaminobenzaldehyde 在 lithium aluminium tetrahydride 、 Kryptofix [2.2.2] 、 ammonium acetate 、 溶剂黄146 、 diborane(6) 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 0.3h， 生成 (4-[¹⁸F]fluoro-m-hydroxyphenethyl)guanidine
  参考文献：
  名称：

  Synthesis and bioevaluation of [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG): A novel radiotracer for quantitative PET studies of cardiac sympathetic innervation

  摘要：

  A new cardiac sympathetic nerve imaging agent, [F-18]4-fluoro-m-hydroxyphenethylguanidine ([F-18]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [F-18]4-fluoro-m-tyramine ([F-18]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [F-18]4F-MHPG. Initial bioevaluations of [F-18]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [C-11]4F-MHPG. The neuronal uptake rate of [F-18]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T-1/2 > 13 h). A PET imaging study in a nonhuman primate with [F-18]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80-90 min after injection of 5-to-1. These initial kinetic and imaging studies of [F-18]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.106

文献信息

• Improved synthesis of 4-[¹⁸ F]fluoro-<i>m</i> -hydroxyphenethylguanidine using an iodonium ylide precursor
  作者：Yong-Woon Jung、Guie Gu、David M. Raffel

  DOI：10.1002/jlcr.3791

  日期：2019.10

  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-[18F]fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG) and 3-[18F]fluoro-p-hydroxyphenethylguanidine ([18F]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 [18F]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 [18F]4F-MHPG to PET centers without on-site radiochemistry facilities.

  在我们的实验室中，最近开发了氟-18标记羟基苯乙基胍作为一种新型PET放射药物，用于量化心脏疾病患者的区域性心脏交感神经密度。对人类受试者进行的4-[18F]氟-m-羟基苯乙基胍（[18F]4F-MHPG）和3-[18F]氟-p-羟基苯乙基胍（[18F]3F-PHPG）的研究显示，这些放射性示踪剂可以使用Patlak图形法生成区域性交感神经密度的高分辨率图谱。以前这些化合物是使用碘盐前体合成的，这为现场临床PET研究提供了足够的放射化学产率。然而，我们对探索能够提供显著更高放射化学产率的新方法感兴趣。螺环碘离子碱前体最近被确立为电子富含芳香化合物放射氟化的新方法，相较于碘盐前体，具备多个优势。本研究的目标是制备螺环碘离子碱前体，以合成[18F]4F-MHPG，并评估其在该放射药物生产中的有效性。在优化的自动反应条件下，碘离子碱前体的放射化学产率平均为7.8% ± 1.4%（n = 8，EOS，未进行衰变校正），约为之前使用碘盐前体合成的产率的三倍。通过进一步优化和规模化，这一方法有可能支持[18F]4F-MHPG的商业分发，向没有现场放射化学设施的PET中心提供服务。
• [¹⁸F]Fluoro-Hydroxyphenethylguanidines: Efficient Synthesis and Comparison of Two Structural Isomers as Radiotracers of Cardiac Sympathetic Innervation
  作者：Yong-Woon Jung、Keun Sam Jang、Guie Gu、Robert A. Koeppe、Phillip S. Sherman、Carole A. Quesada、David M. Raffel

  DOI：10.1021/acschemneuro.7b00051

  日期：2017.7.19

  report an efficient synthesis of 18F-hydroxyphenethylguanidines consisting of nucleophilic aromatic [18F]fluorination of a protected diaryliodonium salt precursor followed by a single deprotection step to afford the desired radiolabeled compound. This approach has been shown to reliably produce 4-[18F]fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) and its structural isomer 3-[18F]fluoro-p-

  氟18标记的苯乙基胍目前正在我们的实验室中开发，作为放射性示踪剂，用于使用PET成像技术定量局部心脏交感神经密度。在这项研究中，我们报告了一种18 F-羟基苯乙基胍的有效合成方法，该方法由受保护的二芳基碘鎓盐前体的亲核芳族[ 18 F]氟化反应组成，然后再进行单个脱保护步骤，即可得到所需的放射性标记化合物。这种方法已被证明可靠地产生4- [ 18 F]氟-米-hydroxyphenethylguanidine（[ 18 F] 4F-MHPG，[ 18 F] 1）和其结构异构体的3- [ 18 F]氟- p-羟基苯乙基胍（[ 18 F] 3F-PHPG，[ 18 F] 2）具有良好的放射化学收率。在非人类灵长类动物中进行[ 18 F] 2的临床前评价，以比较其与先前使用[ 18 F] 1获得的成像特性，代谢和心肌动力学。这些研究的结果表明[ 18 F] 2表现出与[ 18 F] 1相当的成像
• 4-[¹⁸F]Fluoro-<i>m</i>-hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography
  作者：Keun Sam Jang、Yong-Woon Jung、Guie Gu、Robert A. Koeppe、Phillip S. Sherman、Carole A. Quesada、David M. Raffel

  DOI：10.1021/jm400770g

  日期：2013.9.26

  4-[18F]Fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic

  4- [ 18 F]氟-米-hydroxyphenethylguanidine（[ 18 F] 4F-MHPG，[ 18 F] 1）是一种新的心交感神经放射性示踪剂与用于量化与PET和示踪剂动力学分析区域神经密度有利动力学性质。的[自动化合成18 F] 1被开发，其中所述中间体4- [ 18 F]氟-米-tyramine（[ 18 F] 16）使用二芳基碘盐前体为亲核芳族[制备18 F]氟化。在恒河猴的 PET 成像研究中，[ 18 F] 1展示了高质量的心脏图像，肺和肝脏摄取低。[ 18 F] 1动力学的房室建模提供了净吸收速率常数K i (mL/min/g 湿)，并且[ 18 F] 1动力学的Patlak图形分析提供了Patlak斜率K p (mL/min/g)。在去甲肾上腺素转运蛋白抑制剂地昔帕明 (DMI) 的药理学阻断研究中，随着 DMI 剂量的增加，这些定量指标中的每一个都以剂量依赖性方式下降。这些初步结果强烈表明
• 心脏显像正电子药物[¹⁸F]MFBG和[¹⁸F]MHPG的新型制备方法
  申请人：王璐

  公开号：CN112778163A

  公开（公告）日：2021-05-11

  本发明公开了心脏显像正电子药物[18F]MFBG和[18F]MHPG的新型制备方法，包括MFBG及MHPG对应核心骨架的芳基碘化合物的合成，对应关键高价碘叶立德前体的结构与合成，以及利用该类前体实现18F标记MFBG及MHPG的方法。本发明要解决的技术问题是提供[18F]MFBG和[18F]MHPG的无载体放射性氟‑18负离子新型标记合成方法，具体为采用两种不同的高价碘叶立德前体进行放射化学反应。此方法步骤少、产率高、操作简便、重复性好、且可自动化生产；应用此方法合成的放射性示踪剂[18F]MFBG和[18F]MHPG的比活度高，化学纯度与放射纯度高，符合注射使用正电子药物的质量标准，对实现PET心脏影像临床推广有重要价值。
• Synthesis and bioevaluation of [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG): A novel radiotracer for quantitative PET studies of cardiac sympathetic innervation
  作者：Keun Sam Jang、Yong-Woon Jung、Phillip S. Sherman、Carole A. Quesada、Guie Gu、David M. Raffel

  DOI：10.1016/j.bmcl.2013.01.106

  日期：2013.3

  A new cardiac sympathetic nerve imaging agent, [F-18]4-fluoro-m-hydroxyphenethylguanidine ([F-18]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [F-18]4-fluoro-m-tyramine ([F-18]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [F-18]4F-MHPG. Initial bioevaluations of [F-18]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [C-11]4F-MHPG. The neuronal uptake rate of [F-18]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T-1/2 > 13 h). A PET imaging study in a nonhuman primate with [F-18]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80-90 min after injection of 5-to-1. These initial kinetic and imaging studies of [F-18]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents. (C) 2013 Elsevier Ltd. All rights reserved.