(S)-2,2',2'',2'''-(2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid | 1020407-41-3

• 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: (S)-2,2',2'',2'''-(2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid
• 英文别名: (S)-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid；(S)-p-SCN-Bn-DOTA；2-[(6S)-4,7,10-tris(carboxymethyl)-6-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• CAS: 1020407-41-3
• 化学式: C₂₄H₃₃N₅O₈S
• 分子量: 551.621
• InChiKey: UDOPJKHABYSVIX-FQEVSTJZSA-N

物化性质

• 沸点：
  826.9±65.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -7.2
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  207
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (S)-2,2',2'',2'''-(2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid 、 碘海醇 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到p-SCN-Bn-DOTA-iohexol
  参考文献：
  名称：

  Poly(iohexol) Nanoparticles As Contrast Agents for in Vivo X-ray Computed Tomography Imaging

  摘要：

  Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanopartides exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

  DOI：

  10.1021/ja405196f

文献信息

• Synthesis of Site-Specific Radiolabeled Antibodies for Radioimmunotherapy via Genetic Code Expansion
  作者：Yiming Wu、Hua Zhu、Bo Zhang、Fei Liu、Jingxian Chen、Yufei Wang、Yan Wang、Ziwei Zhang、Ling Wu、Longlong Si、Huan Xu、Tianzhuo Yao、Sulong Xiao、Qing Xia、Lihe Zhang、Zhi Yang、Demin Zhou

  DOI：10.1021/acs.bioconjchem.6b00412

  日期：2016.10.19

  conjugated to the antibody through cysteine or lysine residues, resulting in heterogeneous chelate-to-antibody ratios and various conjugation sites. To overcome this heterogeneity, we have developed an approach for site-specific radiolabeling of antibodies by combination of genetic code expansion and click chemistry. As a proof-of-concept study, model systems including anti-CD20 antibody rituximab, positron-emitting

  放射免疫疗法（RIT）通过单抗体将放射性同位素传递给表达抗原的细胞，以对病灶成像或进行药物治疗。螯合物通常通过半胱氨酸或赖氨酸残基与抗体缀合，从而导致异种螯合物与抗体的比例和各种缀合位点。为了克服这种异质性，我们开发了一种通过遗传密码扩展和点击化学相结合的方法对抗体进行位点特异性放射性标记的方法。作为概念验证研究，包括抗CD20抗体利妥昔单抗，正电子发射同位素64的模型系统铜和新合成的双功能连接基（4-dibenzocyclooctynynol–1,4,7,10-四氮杂环十四烷-1,4,7,10-四乙酸，DIBO–DOTA）被使用。该方法包括三个步骤：（1）通过遗传密码扩展技术在抗体的定义位点将带有叠氮基的氨基酸（NEAK）进行位点特异性掺入，作为“化学处理”；（2）在温和条件下双功能接头与抗体的位点特异性和定量缀合；（3）用适当的同位素对螯合物修饰的抗体进行放射性标记。我们使用重链A12
• Aptamer-Functionalized, Ultra-Small, Monodisperse Silica Nanoconjugates for Targeted Dual-Modal Imaging of Lymph Nodes with Metastatic Tumors
  作者：Li Tang、Xujuan Yang、Lawrence W. Dobrucki、Isthier Chaudhury、Qian Yin、Catherine Yao、Stéphane Lezmi、William G. Helferich、Timothy M. Fan、Jianjun Cheng

  DOI：10.1002/anie.201205271

  日期：2012.12.14

  dual‐modal imaging probe based on size‐controlled silica nanoconjugates was synthesized for targeted imaging of lymph nodes by means of both PET and near infrared fluorescence techniques. 20 nm nanoconjugates (see scheme) functionalized with an aptamer (green triangles) that targets 4T1 breast cancer cells improved the detection efficiency of sentinel lymph nodes with metastatic tumors.

  合成了一种基于尺寸控制的二氧化硅纳米缀合物的双模态成像探针，用于通过 PET 和近红外荧光技术对淋巴结进行靶向成像。 20 nm 纳米缀合物（参见方案）与靶向 4T1 乳腺癌细胞的适体（绿色三角形）功能化，提高了转移性肿瘤前哨淋巴结的检测效率。
• Preclinical evaluation of new GnRH-I receptor radionuclide therapy with ¹⁷⁷ Lu-peptide tracer
  作者：Masoumeh Zoghi、Sima Attar Nosrati、Faramarz Rogni、Gholamhossein Shirvani、Fariba Johari Daha

  DOI：10.1002/jlcr.3742

  日期：2019.6.15

  this study was to develop preclinical evaluation of a novel radiolabeled gonadotropin-releasing hormone (GnRH) receptor targeting peptide for prostate cancer therapy. The new antiproliferative agent of GnRH-I analogue was developed on the basis of the D-Trp6 -GnRH-I scaffold, and in vivo pharmacokinetics and receptor binding affinity were enhanced by the substitution of Gly-NHNH2 for Gly-NH2 at position

  本研究的目的是对用于前列腺癌治疗的新型放射性标记促性腺激素释放激素 (GnRH) 受体靶向肽进行临床前评估。GnRH-I类似物的新型抗增殖剂是在D-Trp6-GnRH-I支架的基础上开发的，通过用Gly-NHNH2取代第10位的Gly-NH2增强了体内药代动力学和受体结合亲和力。 D-Trp6 -GnRH-I。为了评估 177 Lu-DOTA-曲普瑞林-酰肼作为肿瘤放射性核素治疗，进行了质量控制测试和临床前阶段评估。采用固相法合成新肽。肽的表征和纯度通过质谱和高效液相色谱 (HPLC) 进行。为了用于靶向治疗，新的 GnRH-I 激动剂与 pSCN-Bn-DOTA 结合使用。然后通过制备型HPLC纯化DOTA-曲普瑞林-酰肼的粗沉淀物。在最佳时间、温度、配体量和镥含量条件下，DOTA-曲普瑞林-酰肼用177 Lu（比活不小于925 GBq/mg）标记。以三种不同方式对 177 Lu-DOTA-TRPHYD
• Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes
  作者：Hiroyuki Suzuki、Mari Araki、Kouki Tatsugi、Kento Ichinohe、Tomoya Uehara、Yasushi Arano

  DOI：10.1021/acs.jmedchem.3c00258

  日期：2023.7.13

  The interposition of a cleavable linkage by enzymes on the renal brush border membrane constitutes a promising approach for reducing the renal radioactivity levels of radiolabeled low-molecular-weight antibody fragments and constructs (LMW Abs). Herein, we applied the molecular design to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-based reagents for radiotheranostic applications

  通过酶在肾刷状缘膜上插入可裂解连接构成了降低放射性标记的低分子量抗体片段和构建体（LMW Abs）的肾脏放射性水平的有前途的方法。在此，我们将分子设计应用于基于 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸 (DOTA) 的试剂，用于三价放射性金属的放射治疗应用。DOTA或其衍生物通过FGK键缀合至Fab（[ 111 In]In-DO3A i Bu-Bn-FGK-Fab或[ 111 In]In-DOTA-Bn-FGK-Fab）。当注射到小鼠体内时，两者均通过血管紧张素转换酶以相似的速率产生放射性代谢物，[ 111 In]In-DO3A i Bu-Bn-F 和 [ 111 In]In-DOTA-Bn-F。两者均表现出比通过常规程序制备的111 In-标记的Fab（[ 111 In]In-DOTA-Bn-SCN-Fab）显着更低的肾放射性水平。每种放射性代谢物从肾脏的消除率不同，显着影响肾脏放射性水平。[
• Synthesis and preliminary in vitro evaluation of DOTA-Tenatumomab conjugates for theranostic applications in tenascin expressing tumors
  作者：Giuseppe Giannini、Ferdinando Maria Milazzo、Gianfranco Battistuzzi、Antonio Rosi、Anna Maria Anastasi、Fiorella Petronzelli、Claudio Albertoni、Lorenzo Tei、Loredana Leone、Laura Salvini、Rita De Santis

  DOI：10.1016/j.bmc.2019.05.047

  日期：2019.8

  Tenatumomab is an anti-tenascin murine monoclonal antibody previously used in clinical trials for delivering radionuclides to tumors by both pre-targeting (biotinylated Tenatumomab within PAGRIT) and direct (131)Iodine labeling approaches. Here we present the synthesis and in vitro characterization of three Tenatumomab conjugates to bifunctional chelating agents (NHS-DOTA, NCS-DOTA and NCS-DTPA). Results indicate ST8198AA1 (Tenatumomab-DOTAMA, derived by conjugation of NHS-DOTA), as the most promising candidate in terms of conjugation rate and yield, stability, antigen immunoreactivity and affinity. Labeling efficiency of the different chelators was investigated with a panel of cold metals indicating DOTAMA as the best chelator. Labeling of Tenatumomab-DOTAMA was then optimized with several metals and stability performed confirms suitability of this conjugate for further development. ST8198AA1 represents an improvement of the previous antibody forms because the labeling with radionuclides like Lu-177 or Cu-64 would allow theranostic applications in patients bearing tenascin expressing tumors.