(211At)astatanyl(211At)astatine-211

• 分子结构分类: 无机化合物 - 均质非金属化合物 - 均相卤素
• 英文名称: (211At)astatanyl(211At)astatine-211
• 化学式: At₂
• 分子量: 422.0
• InChiKey: BSXAZQBJJWCDAY-ZDOIIHCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.0
• 重原子数：
  2
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (((S)-1-(tert-butoxy)-1,5-dioxo-5-((4-(tributylstannyl)phenethyl)amino)pentan-2-yl)carbamoyl)-L-glutamate 、 (211At)astatanyl(211At)astatine-211 在 N-氯代丁二酰亚胺 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Synthesis and preliminary evaluation of 211At-labeled inhibitors of prostate-specific membrane antigen for targeted alpha particle therapy of prostate cancer

  摘要：

  DOI：

  10.1016/j.nucmedbio.2021.01.002
• 作为试剂：
  描述：

  C₄₅H₆₈N₈O₁₃SSn 、 三氟乙酸 在 N-氯代丁二酰亚胺 、 (211At)astatanyl(211At)astatine-211 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 C₃₂H₄₃⁽²¹¹⁾AtN₈O₉S*C₂HF₃O₂
  参考文献：
  名称：

  使用新型残留修复剂对 HER2 靶向单域抗体片段进行位点特异性放射性卤化

  摘要：

  由于其快速的肿瘤积累和正常的组织清除，单域抗体片段 (sdAb) 是开发用 α 发射体 211 At 标记的放射治疗剂的有吸引力的载体。在此，我们评估了iso -[ 211 At]AGMB-PODS，这是一种修复剂，它结合了残留放射性卤素的功能和用于位点特异性 sdAb 缀合的苯恶二唑基甲基砜 (PODS) 部分。异-[ 211At]AGMB-PODS 及其放射性碘化类似物被评估用于与带有 C 末端 GGC 尾巴的抗 HER2 5F7 sdAb 的硫醇选择性缀合。两种放射性卤化的 PODS-5F7GGC 偶联物都以良好的放射化学产率合成，并且对 HER2 阳性 BT474 乳腺癌细胞保持高结合亲和力。在半胱氨酸和人血清白蛋白 (HSA) 存在的情况下，异-[ 211 At]AGMB-PODS-5F7GGC在体外比其马来酰亚胺类似物稳定得多，并且表现出出色的肿瘤摄取和高体内稳定性。与 [ 177

  DOI：

  10.1021/acs.jmedchem.2c01331

文献信息

• Preclinical evaluation of new α-radionuclide therapy targeting LAT1: 2-[211At]astato-α-methyl-L-phenylalanine in tumor-bearing model
  作者：Yasuhiro Ohshima、Hiroyuki Suzuki、Hirofumi Hanaoka、Ichiro Sasaki、Shigeki Watanabe、Hiromitsu Haba、Yasushi Arano、Yoshito Tsushima、Noriko S. Ishioka

  DOI：10.1016/j.nucmedbio.2020.08.003

  日期：2020.11

  Introduction: Targeted α-radionuclide therapy has attracted attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared an LAT1-selective α-radionuclide-labeled amino acid analog, 2-[²¹¹At]astato-α-methyl-L-phenylalanine (2-[²¹¹At]AAMP), and evaluated its potential as a therapeutic agent. Methods: 2-[²¹¹At]AAMP was prepared from the stannyl precursor. Stability of 2-[²¹¹At]AAMP was evaluated both in vitro and in vivo. In vitro studies using an LAT1-expressing human ovarian cancer cell line, SKOV3, were performed to evaluate cellular uptake and cytotoxicity of 2-[²¹¹At]AAMP. Biodistribution and therapeutic studies in SKOV3-bearing mice were performed after intravenous injection of 2-[²¹¹At]AAMP. Results: 2-[²¹¹At]AAMP was stable in murine plasma in vitro and excreted intact into urine. Cellular uptake of 2-[²¹¹At]AAMP was inhibited by treatment with an LAT1-selective inhibitor. After 24 h incubation, 2-[²¹¹At]AAMP suppressed clonogenic growth at 10 kBq/ml, and induced cell death and DNA double-strand breaks at 25 kBq/ml. When injected into mice, 2-[²¹¹At]AAMP exhibited peak accumulation in the tumor at 30 min postinjection, and radioactivity levels in the tumor were retained up to 60 min. The majority of the radioactivity was rapidly eliminated from the body into urine in an intact form immediately after injection. 2-[²¹¹At]AAMP significantly improved the survival of mice (P < 0.05) without serious side effects. Conclusion: 2-[²¹¹At]AAMP showed α-radiation-dependent cellular growth inhibition after it was taken up via LAT1. In addition, 2-[²¹¹At]AAMP had a beneficial effect on survival in vivo. These findings suggest that 2-[²¹¹At]AAMP would be useful for the treatment of LAT1-positive cancer. Advances in knowledge and implications for patient care: This is the first report of an LAT1-targeting radiopharmaceutical for α-radionuclide therapy; this agent would be applicable for the treatment of various types of cancer.
• Synthesis and preliminary evaluation of 211At-labeled inhibitors of prostate-specific membrane antigen for targeted alpha particle therapy of prostate cancer
  作者：Ganesan Vaidyanathan、Ronnie C. Mease、Il Minn、Jaeyeon Choi、Ying Chen、Hassan Shallal、Choong Mo Kang、Darryl McDougald、Vivek Kumar、Martin G. Pomper、Michael R. Zalutsky

  DOI：10.1016/j.nucmedbio.2021.01.002

  日期：2021.3