N-[2-(4-¹⁸F-fluorobenzamido)ethyl]maleimide | 929706-89-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-(4-¹⁸F-fluorobenzamido)ethyl]maleimide
• 英文别名: N-[2-(2,5-dioxopyrrol-1-yl)ethyl]-4-(18F)fluoranylbenzamide
• CAS: 929706-89-8
• 化学式: C₁₃H₁₁FN₂O₃
• 分子量: 261.242
• InChiKey: ICZJTINEUOFDLT-UMSOTBISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(4-¹⁸F-fluorobenzamido)ethyl]maleimide 、 Cys-pipGly-Pro-pipAmGly-Arg-Pro-Tyr-tBuGly-Leu-OH 以 aq. phosphate buffer 为溶剂， 反应 0.25h， 以90%的产率得到
  参考文献：
  名称：

  [EN] VINYLSULFONE-BASED 18F-LABELING COMPOSITIONS AND METHODS AND USES THEREOF
  [FR] COMPOSITION DE MARQUAGE AU 18F À BASE DE VINYLSULFONE ET PROCÉDÉS ET UTILISATIONS ASSOCIÉS

  摘要：

  一种硫选择性放射性标记试剂具有以下一般公式：*R-L-VS，其中*R是放射性同位素，L是连接基团，VS是乙烯磺酮官能团，其中所述标记试剂能够共价结合到含有巯基的生物分子，如蛋白质或肽。还公开了使用所述标记试剂标记神经肽素及其变体的方法。

  公开号：

  WO2014138720A1
• 作为产物：
  描述：

  (2,3,4,5,6-pentamethylphenyl)methyl 4-(18F)fluoranylbenzoate 在 氰基磷酸二乙酯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 反应 0.08h， 生成 N-[2-(4-¹⁸F-fluorobenzamido)ethyl]maleimide
  参考文献：
  名称：

  WO2008/118601

  摘要：

  公开号：

文献信息

• Fully automated synthesis and coupling of [¹⁸F]FBEM to glutathione using the iPHASE FlexLab module
  作者：Uwe Ackermann、Lucie Plougastel、Christian Wichmann、Yit Wooi Goh、Shinn Dee Yeoh、Stan S. Poniger、Henri J. Tochon-Danguy、Andrew M. Scott

  DOI：10.1002/jlcr.3175

  日期：2014.2

  Site-specific radiolabelling of peptides or antibodies using [18F]FBEM is often preferred over non-site-specific radiolabelling with [18F]SFB because it does not affect the affinity of the antibody to its target. Unfortunately, the synthesis of [18F]FBEM and its conjugation to thiol containing macromolecules requires some manual intervention, which leads to radiation exposure of the radiochemist. In this publication, we report on the complete automation of [18F]FBEM production and its subsequent conjugation to glutathione using a slightly modified iPHASE FlexLab module. [18F]FBEM was produced in 1.185 ± 0.168 GBq (15–20%; n = 10; 0.75 ± 0.106 GBq non-decay corrected) with a specific activity of 57 ± 10 GBq/µmol. Radiochemical purity was 97 ± 1% and the synthesis time including HPLC purification and reformulation was 70 min. After evaporation to dryness, [18F]FBEM was conjugated to glutathione in PBS buffer pH 7.4 in quantitative yields. This fully automated method does not require any manual intervention and therefore reduces the radiation exposure to the operator.

  使用[18F]FBEM对肽或抗体进行特定位点放射性标记通常比使用[18F]SFB进行非特定位点放射性标记更可取，因为前者不会影响抗体与其靶标的亲和力。遗憾的是，[18F]FBEM的合成及其与含硫醇大分子的偶联需要人工干预，这会导致放射化学家受到辐射。在本出版物中，我们报告了使用经过轻微修改的iPHASE FlexLab模块实现[18F]FBEM生产及其后续与谷胱甘肽偶联的完全自动化。[18F]FBEM的生产量为1.185 ± 0.168 GBq（15-20%；n = 10；0.75 ± 0.106 GBq非衰变校正），比活度为57 ± 10 GBq/µmol。放射化学纯度为97 ± 1%，包括HPLC纯化和重新配制在内的合成时间为70分钟。在蒸发至干燥后，[18F]FBEM在pH 7.4的PBS缓冲液中与谷胱甘肽定量偶联。这种全自动方法不需要任何人工干预，因此减少了操作员的辐射暴露。
• Design and Synthesis of an Easily Obtainable Maleimide Reagent <i>N</i>-[2-(4-[¹⁸F]fluoro-<i>N</i>-methylbenzenesulfonamido)ethyl]maleimide ([¹⁸F]FBSEM) to Radiolabel Thiols in Proteins
  作者：Yuji Fujita、Yoshihiro Murakami、Akihiro Noda、Sosuke Miyoshi

  DOI：10.1021/acs.bioconjchem.6b00707

  日期：2017.2.15

  reagent [18F]FBSEM (N-[2-(4-[18F]fluoro-N-methylbenzenesulfonamido)ethyl]maleimide) was developed. The advantage of the design is that the precursor and [18F]FBSEM have the same backbone and backbone construction is not required; in contrast, known thiol-specific labeling reagents do require backbone construction, and this is thought to be the cause of their complicated synthesis. [18F]FBSEM was successfully

  开发了一种易于获得的硫醇选择性标记试剂[ 18 F] FBSEM（N- [2-（4- [ 18 F]氟-N-甲基苯磺酰胺基）乙基]马来酰亚胺）。该设计的优点是前体和[ 18 F] FBSEM具有相同的主链，并且不需要主链结构。相反，已知的硫醇特异性标记试剂确实需要骨架结构，这被认为是其复杂合成的原因。[ 18 F] FBSEM成功在更高的产率（25％）获得，并且以更简单的方式（二氟化和脱保护步骤在65分钟）比目前广泛使用的[ 18 F] FBEM（ñ - [2-（4- [ 18F]氟苯甲酰胺）乙基]马来酰亚胺）。[ 18 F] FBSEM的标记功效通过与谷胱甘肽结合而得到证实。[ 18 F] FBSEM是一种有前途的蛋白质标记剂。
• Preliminary Biological Evaluation of 18F-FBEM-Cys-Annexin V a Novel Apoptosis Imaging Agent
  作者：Chunxiong Lu、Quanfu Jiang、Minjin Hu、Cheng Tan、Huixin Yu、Zichun Hua

  DOI：10.3390/molecules20034902

  日期：——

  A novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at its C-terminal has been developed and successfully labeled site-specifically with 18F-FBEM. 18F-FBEM was synthesized by coupling 18F-fluorobenzoic acid (18F-FBA) with N-(2-aminoethyl)maleimide using optimized reaction conditions. The yield of 18F-FBEM-Cys-Annexin V was 71.5% ± 2.0% (n = 4, based on the starting 18F-FBEM, non-decay corrected). The radiochemical purity of 18F-FBEM-Cys-Annexin V was >95%. The specific radioactivities of 18F-FBEM and 18F-FBEM-Cys-Annexin V were >150 and 3.17 GBq/µmol, respectively. Like the 1st generation 18F-SFB-Annexin V, the novel 18F-FBEM-Cys-Annexin V mainly shows renal and to a lesser extent, hepatobiliary excretion in normal mice. In rat hepatic apoptosis models a 3.88 ± 0.05 (n = 4, 1 h) and 10.35 ± 0.08 (n = 4, 2 h) increase in hepatic uptake of 18F-FBEM-Cys-Annexin V compared to normal rats was observed after injection via the tail vein. The liver uptake ratio (treated/control) at 2 h p.i. as measured via microPET correlated with the ratio of apoptotic nuclei in liver observed using TUNEL histochemistry, indicating that the novel 18F-FBEM-Cys-Annexin V is a potential apoptosis imaging agent.

  我们开发了一种新型附件素 V 衍生物（Cys-Annexin V），其 C 端只有一个半胱氨酸残基，并成功地用 18F-FBEM 进行了位点特异性标记。18F-FBEM 是由 18F- 氟苯甲酸（18F-FBA）与 N-（2-氨基乙基）马来酰亚胺在优化的反应条件下偶联合成的。18F-FBEM-Cys-Annexin V 的产率为 71.5% ± 2.0%（n = 4，基于起始 18F-FBEM，非衰变校正）。18F-FBEM-Cys-Annexin V 的放射化学纯度大于 95%。18F-FBEM 和 18F-FBEM-Cys-Annexin V 的比放射活性分别大于 150 GBq/µmol 和 3.17 GBq/µmol。与第一代 18F-SFB-Annexin V 一样，新型 18F-FBEM-Cys-Annexin V 在正常小鼠体内主要通过肾脏排泄，其次是肝胆排泄。在大鼠肝细胞凋亡模型中，经尾静脉注射 18F-FBEM-Cys-Annexin V 后，与正常大鼠相比，肝摄取量分别增加了 3.88 ± 0.05（n = 4，1 小时）和 10.35 ± 0.08（n = 4，2 小时）。通过 microPET 测定的肝脏摄取比率（处理/对照）与使用 TUNEL 组织化学法观察到的肝脏凋亡细胞核比率相关，表明新型 18F-FBEM-Cys-Annexin V 是一种潜在的细胞凋亡成像剂。
• Methods and Compositions for Improved F-18 Labeling of Proteins, Peptides and Other Molecules
  申请人：Immunomedics, Inc.

  公开号：US20140017168A1

  公开（公告）日：2014-01-16

  The present application discloses compositions and methods of synthesis and use of 18 F or 19 F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18 F or 19 F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18 F or 19 F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

  本申请公开了用于PET、SPECT和/或MR成像的18F或19F标记分子的合成和使用方法。优选地，通过与III A族金属形成复合物，并将复合物与双官能团螯合剂结合，将18F或19F结合到靶向分子上。在其他实施例中，18F或19F标记的部分可以包括可靶向的构造物，与双特异性抗体结合以靶向疾病相关抗原。所公开的方法和组合物允许在30分钟内以非常高的效率和特异活性简单和可重复地标记分子。在优选实施例中，标记的分子可以在标记后无需纯化即可用于主体成像。
• 18F-Labeled wild-type annexin V: comparison of random and site-selective radiolabeling methods
  作者：Amanda Perreault、James C. Knight、Monica Wang、Jenilee Way、Frank Wuest

  DOI：10.1007/s00726-015-2068-0

  日期：2016.1

  Early stage apoptosis is characterized by the externalization of phosphatidylserine (PS) from the inner leaflet of the plasma membrane to the outer periphery. Consequently, PS represents an excellent target for non-invasive imaging of apoptosis by positron emission tomography. Annexin V is a 36 kDa protein which binds with high affinity to PS. Radiolabeling of wild-type annexin V with fluorine-18 (F-18) can be accomplished via random acylation of 23 amine groups (22 lysine residues and one N-terminal amine) with [F-18]SFB or site-specific alkylation reaction on cysteine residue at position 315 with maleimide-containing prosthetic groups like [F-18]FBEM. The effect upon random and site-directed F-18 labeling of annexin V was studied with EL4 mouse lymphoma cells. Both, randomly and site-selectively radiolabeled annexin V demonstrated comparable binding to apoptotic EL4 cells. This finding suggests that the F-18 radiolabeling method has no significant effect on the ability of F-18-labeled wild-type annexin V to bind PS in apoptotic cells.