(67)gallium citrate | 41183-64-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (67)gallium citrate
• 英文别名: gallium-67 citrate；⁶⁷Ga-citrate；[67Ga]citrate；Gallium Citrate Ga-67；gallium-67(3+);2-hydroxypropane-1,2,3-tricarboxylate
• CAS: 41183-64-6
• 化学式: C₆H₅O₇*Ga
• 分子量: 256.101
• InChiKey: YEEGWNXDUZONAA-RYDPDVNUSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -5.63
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：本记录中的信息是指将镓67柠檬酸盐用作诊断剂。几项国际指南建议在镓67柠檬酸盐使用后停止哺乳3到4周或完全停止哺乳。如果母亲希望恢复哺乳，在哺乳中断期间应定期且完全排空乳房。如果母亲在检查前已经表达并储存了乳汁，她可以在哺乳中断期间喂给婴儿。母亲在哺乳中断期间泵出的乳汁可以丢弃，或者冷冻储存，在经过10个物理半衰期，大约33天后，再喂给婴儿。 担心乳汁中放射性水平的母亲可以要求在医院核医学科进行检测。当放射性水平达到安全水平时，她可以恢复哺乳。已经发布了一种测量乳汁放射性并确定母亲可以安全恢复哺乳的时间的方法。接受小于190 MBq剂量进行炎症扫描的母亲无需避免与婴儿密切接触。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关已发布信息。 ◉ 对泌乳和乳汁的影响：截至修订日期，未找到相关已发布信息。

◉ Summary of Use during Lactation:Information in this record refers to the use of Ga 67 citrate as a diagnostic agent. Several international guidelines recommend discontinuation of breastfeeding for 3 to 4 weeks or complete cessation of breastfeeding after Ga 67 citrate. If the mother wishes to resume nursing, the breasts should be emptied regularly and completely during the period of interruption. If the mother has expressed and saved milk prior to the examination, she can feed it to the infant during the period of nursing interruption. The milk that is pumped by the mother during the time of breastfeeding interruption can either be discarded or stored frozen and given to the infant after 10 physical half-lives, or about 33 days, have elapsed. Mothers concerned about the level of radioactivity in their milk could ask to have it tested at a nuclear medicine facility at their hospital. When the radioactivity is at a safe level, she may resume breastfeeding. A method for measuring milk radioactivity and determining the time when a mother can safely resume breastfeeding has been published. Mothers who receive a dose less than 190 MBq for an inflammation scan need not refrain from close contact with their infants. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 蛋白质结合

镓至少与四种铁结合分子结合：转铁蛋白、乳铁蛋白、铁蛋白和 siderophores。Siderophores 是低分子量的化合物，有助于微生物摄取铁。

Gallium binds to at least four iron-binding molecules: transferrin, lactoferrin, ferritin, and siderophores. Siderophores are compounds of low molecular weight that facilitate iron uptake by microorganisms.

来源:DrugBank

吸收、分配和排泄

• 吸收

身体通常将Ga3+处理得好像它是三价铁（Fe-III）一样。然而，镓在体内无法被还原。因此，三价铁离子很容易被还原并与原卟啉IX相互作用形成血红素，而镓则保持与铁传递蛋白和载体分子结合。

The body generally handles Ga3+ as though it were ferric iron (Fe-III). However, gallium can not be reduced in vivo. Therefore, ferric ion is easily reduced and interacts with protoporphyrin IX to form heme, gallium remains bound to iron-transport proteins and carrier molecules.

来源:DrugBank

吸收、分配和排泄

• 消除途径

无尿液排泄；主要通过粪便排泄消除。

No urinary excretion; elimination primarily via fecal excretion.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸 、 (67)gallium citrate 以 aq. acetate buffer 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  CONJUGATES AND THEIR USES IN MOLECULAR IMAGING

  摘要：

  本发明涉及双功能化合物，该双功能化合物用于分子成像和治疗，使用该双功能化合物进行分子成像的方法以及包括用于分子成像的双功能化合物的试剂盒。这些双功能化合物具有三脚架羟基吡啶酮螯合部分，并且可以与靶向基团偶联，以使化合物靶向主体中的特定细胞或组织。

  公开号：

  US20140056810A1

文献信息

• Coordination-Mediated Synthesis of ⁶⁷Ga-Labeled Purification-Free Trivalent Probes for in Vivo Imaging of Saturable Systems
  作者：Holis A. Holik、Tomoya Uehara、Soki Nemoto、Takemi Rokugawa、Yuumi Tomizawa、Ayako Sakuma、Yuki Mizuno、Hiroyuki Suzuki、Yasushi Arano

  DOI：10.1021/acs.bioconjchem.8b00337

  日期：2018.9.19

  A large excess of unlabeled ligands over gallium-67 (67Ga) provides 67Ga-labeled probes with high radiochemical yields in a short reaction time. However, the unlabeled ligands hinder target accumulation of radiolabeled probes by competing for target molecules. To circumvent the problem, we investigated the way to prepare 67Ga-labeled multivalent probes from monovalent ligands. The reaction of a bi- or tridentate ligand with [67Ga]Ga-citrate resulted in 67Ga-labeled probes of insufficient stability. However, the reaction of [67Ga]Ga-citrate with a mixture of RGD-conjugated salicylaldehyde and triamine provided a 67Ga-labeled trivalent probe with stability sufficient for in vivo applications. Since the free Schiff base ligand decomposed rapidly upon injection, the 67Ga-labeled trivalent probe visualized the murine tumor without postlabeling purification, which was not achieved with a 67Ga-labeled trivalent probe from a trivalent ligand. These findings indicate the availability of Schiff base ligands to prepare 67Ga-labeled trivalent probes by a simple radiolabeling procedure.

  大量未标记的配体相对于镓-67 (67Ga) 的过量提供了在短时间内获得高放射化学产率的67Ga标记探针。然而，未标记的配体通过竞争靶分子而妨碍了放射性标记探针的靶向聚集。为了解决这个问题，我们研究了如何从单价配体制备67Ga标记的多价探针。双齿或三齿配体与[67Ga]Ga-柠檬酸的反应产生的67Ga标记探针稳定性不足。然而，[67Ga]Ga-柠檬酸与RGD结合的水杨醛和三胺混合物的反应则提供了一种具有足够稳定性用于体内应用的67Ga标记三价探针。由于游离的希夫碱配体在注射后迅速降解，因此67Ga标记的三价探针能够在没有后标记纯化的情况下可视化小鼠肿瘤，而这在由三价配体制备的67Ga标记三价探针中无法实现。这些发现表明希夫碱配体可通过简单的放射性标记程序制备67Ga标记的三价探针。
• ⁶⁷Ga-metalloprobes: monitoring the impact of geometrical isomers on accumulation profiles in rat cardiomyoblasts and human breast carcinoma cells
  作者：Jothilingam Sivapackiam、Scott E. Harpstrite、Nigam P. Rath、Vijay Sharma

  DOI：10.1039/c6md00474a

  日期：——

  similar monocationic gallium(III) complexes and their radiolabeled SPECT counterparts were obtained from Schiff base precursor ligands using ligand exchange reactions to evaluate the impact of cis and trans-isomers on their cellular accumulation profiles in rat cardiomyoblasts (H9c2(2-1)) and human breast carcinoma (MCF-7neo) cells. 67Ga-metalloprobes comprising trans-phenolates showing an overall octahedral

  使用配体交换反应从席夫碱前体配体中获得几何相似的单阳离子镓（III）配合物及其放射性标记的SPECT对应物，以评估顺式和反式异构体对大鼠心肌母细胞（H9c2（2-1））中细胞蓄积谱的影响和人乳腺癌（MCF-7neo）细胞。67种含反式的金属镓-酚盐显示整体八面体的几何形状，并在其分子表面上显示出均匀的正电荷空间分布，在H9c2（2-1）和MCF-7neo细胞中显示稳态积累，并位于细胞的线粒体中。重要的是，具有酚盐顺式排列的替代几何相似和单阳离子金属探针对应物在H9c2（2-1）和MCF-7neo细胞中不显示细胞摄取。利用自己的微薄荧光特征，活细胞成像表明，反式金属lop的β-异构体在其穿透后位于细胞的线粒体内，从而表明放射性示踪剂数据与活细胞显微镜检查结果具有极好的相关性。总体而言，这些结果表明，这类金属大麦的细胞摄取情况是由分子表面上电荷的空间分布和疏水性介导的。
• Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for ⁶⁸Ga PET
  作者：Miguel F. Ferreira、Goretti Pereira、João P. André、M. I. M. Prata、Paula M. T. Ferreira、José A. Martins、Carlos F. G. C. Geraldes

  DOI：10.1039/c4dt00386a

  日期：——

  pH-independent N3O3 coordination in the pH range 3–10 involving the carboxylate group of the pendant propionate arm in a 6 member chelate. For the Ga[NO2A-N-(α-amino)propionate] chelate, a reversible pH-triggered switch from Ga3+ coordination to the carboxylate group to coordination to the amine group of the propionate arm was observed upon pH increase/decrease in the pH range 4–6. This phenomenon can conceivably

  商业化的独立于68 Ge / 68 Ga回旋加速器的68 Ga 3+发生器的问世使大多数医院都可以使用正电子发射断层扫描（PET），这引起了人们对Ga 3双功能螯合剂设计和合成的兴趣激增+。在这项工作中，我们介绍了基于三氮杂环壬烷骨架的NO2A - N-（α-氨基）丙酸螯合剂家族。通过1 H和71 Ga NMR研究了母体NO2A - N-（α-氨基）丙酸螯合剂和低分子量（模型）酰胺共轭物与Ga 3+的络合。Ga 3+酰胺缀合物的螯合物在6-10的螯合物中，在3-10的pH范围内具有非pH依赖性的N 3 O 3配位，涉及丙酸酯侧链的羧酸酯基团。对于Ga [NO2A - N-（α-氨基）丙酸酯]螯合物，在pH升高/降低时，观察到从Ga 3+配位到羧酸酯基到配位到丙酸酯臂的胺基的可逆pH触发转换。 pH范围4–6。可以想到，该现象构成了生理pH传感器的基础。两种复合物在生理范围内都是稳定的。发现[