potassium 4-[18F]fluorobenzoate | 1210779-41-1

• 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: potassium 4-[18F]fluorobenzoate
• CAS: 1210779-41-1
• 化学式: C₇H₄FO₂*K
• 分子量: 177.206
• InChiKey: FIOVWDAWNJVFDJ-IBQICOIKSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.81
• 重原子数：
  11.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.13
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  potassium 4-[18F]fluorobenzoate 以 aq. phosphate buffer 、 乙腈 为溶剂， 反应 0.58h， 生成 (2R)-N-[(2S)-1-[[(2S)-1-amino-6-[(4-(18F)fluoranylbenzoyl)amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-N'-hydroxy-2-(2-methylpropyl)butanediamide
  参考文献：
  名称：

  A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [18F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging

  摘要：

  Background: Numerous clinical studies have shown a correlation between increased matrix metalloproteinase (MMP)/a disintegrin and metalloproteinase (ADAM) activity and poor outcome of cancer. Various MMP inhibitors (MMPIs) have been developed for therapeutic purposes in oncology. In addition, molecular imaging of MMP/ADAM levels in vivo would allow the diagnosis of tumors. We selected the dual inhibitor of MMPs and ADAMs, ML5, which is a hydroxamate-based inhibitor with affinities for many MMPs and ADAMs. ML5 was radiolabelled with F-18 and the newly obtained radiolabelled inhibitor was evaluated in vitro and in vivo.Materials and methods: ML5 was radiolabelled by direct acylation with N-succinimidyl-4-[F-18]fluorobenzoate ([F-18]SFB) for PET (positron emission tomography). The resulting radiotracer [F-18]FB-ML5 was evaluated in vitro in human bronchial epithelium 16HBE cells and breast cancer MCF-7 cells. The non-radioactive probe FB-ML5 and native ML5 were tested in a fluorogenic inhibition assay against MMP-2, -9, -12 and ADAM-17. The in vivo kinetics of [F-18]FB-ML5 were examined in a HT1080 tumor-bearing mouse model. Specificity of probe binding was examined by co-injection of 0 or 2.5 mg/kg ML5. Results: ML5 and FB-ML5 showed high affinity for MMP-2, -9, -12 and ADAM-17; indeed IC50 values were respectively 7.4 +/- 2.0, 19.5 +/- 2.8, 2.0 +/- 0.2 and 5.7 +/- 2.2 nM and 12.5 +/- 3.1, 31.5 +/- 13.7, 138.0 +/- 10.9 and 24.7 +/- 2.8 nM. Radiochemical yield of HPLC-purified [F-18]FB-ML5 was 13-16% (corrected for decay). Cellular binding of [F-18]FB-ML5 was reduced by 36.6% and 27.5% in MCF-7 and 16HBE cells, respectively, after co-incubation with 10 mu M of ML5. In microPET scans, HT1080 tumors exhibited a low and homogeneous uptake of the tracer. Tumors of mice injected with [F-18]FB-ML5 showed a SUVmean of 0.145 +/- 0.064 (n = 6) which decreased to 0.041 +/- 0.027 (n = 6) after target blocking (p < 0.05). Ex vivo biodistribution showed a rapid excretion through the kidneys and the liver. Metabolite assays indicated that the parent tracer represented 23.2 +/- 7.3% (n = 2) of total radioactivity in plasma, at 90 min post injection (p.i.).Conclusion: The nanomolar affinity MMP/ADAM inhibitor ML5 was successfully labelled with F-18. [F-18]FB-ML5 demonstrated rather low binding in ADAM-17 overexpressing cell lines. [F-18]FB-ML5 uptake showed significant reduction in the HT1080 tumor in vivo after co-injection of ML5. [F-18]FB-ML5 may be suitable for the visualization/quantification of diseases overexpressing simultaneously MMPs and ADAMs. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.013
• 作为产物：
  描述：

  4-(乙氧羰基)-N,N,N-三甲基苯铵三氟甲烷磺酸酯 在 potassium tert-butylate 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 为溶剂， 反应 0.04h， 生成 potassium 4-[18F]fluorobenzoate
  参考文献：
  名称：

  MODULAR RADIOCHEMISTRY SYNTHESIS SYSTEM

  摘要：

  一个模块化的化学生产系统包括多个模块，用于从远程位置执行化学反应，特别是放射化学化合物的反应。一个实施例包括一个反应容器，其中包括一个可移动的热源，其相对于反应容器的位置可以从远程位置控制。另一种情况是热源可能固定在某个位置，而反应瓶可以移动进入和移出热源。反应容器有一个或多个密封塞，其相对于反应容器的位置可以从远程位置控制。此外，一个或多个反应容器密封塞可以包括一个或多个通道，用于提供反应物、大气或高压气体、惰性气体、抽真空以及将反应产物从反应瓶中移出和移入，带有密封塞的反应瓶在高压下可操作。该模块化化学生产系统由模块组装而成，每个模块可以包括用于监测和控制各个模块和组装系统的操作条件传感器和控制器，可以从远程位置进行监控和控制。其他模块包括但不限于试剂储存和输送模块、柱层净化模块、微波反应模块、外部质控/分析/净化接口模块、等份取样模块、F-18 干燥模块、浓缩模块、辐射计数模块和毛细管反应器模块。

  公开号：

  US20150329583A1

文献信息

• [EN] SIMPLIFIED ONE-POT SYNTHESIS OF [18F]SFB FOR RADIOLABELING<br/>[FR] SYNTHÈSE MONOTOPE SIMPLIFIÉE DE [18F]SFB POUR RADIOMARQUAGE
  申请人：UNIV CALIFORNIA

  公开号：WO2010033196A3

  公开（公告）日：2010-08-05