模态CCK2R放射性光标志物与mTOR抑制协同,用于增强瘤治疗
Linjie Bian1,2,3,4, Zheyi Wang5,6, Panli Li1,2,3,4
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, shanghai 200032, China.
一种针对胆囊托基宁-2受体 (CCK2R) 的新型二维放射追踪器显示了瘤向和保留的改善. 将这种药物与mTOR抑制相结合,可以提高CCK2R阳性癌症的放射疗效.
科学领域:
- 核医学就是核医学.
- 在瘤学瘤学.
- 分子成像学分子成像学
背景情况:
- 胆囊托基宁-2受体 (CCK2R) 是神经内分泌癌症的关键标,如髓性甲状腺癌和小细胞肺癌.
- 现有的minigastrin类似物显示出对CCK2R向的放射性射有希望.
研究的目的:
- 开发和评估一种新型的二维CCK2R向型放射追踪器,DOTA-CCK2R-dimer.
- 为了研究该剂与mTOR抑制结合的放射敏感化潜力.
主要方法:
- 设计和合成DOTA-CCK2R-dimer. 的设计和合成.
- 用-68 (68Ga) 进行PET成像和用-177 (177Lu) 进行治疗.
- 在体内瘤向评估和与单体标志物进行比较.
- 使用RAD001 (mTOR抑制剂) 的联合治疗.
- 单细胞RNA测序 (scRNA-seq) 用于阐明放射敏感化机制.
主要成果:
- 与其单体对应物相比,DOTA-CCK2R-二元体在体内表现出优异的瘤向和保留.
- [177Lu]Lu-DOTA-CCK2R-二次体选择性地消除了增殖和差分化的瘤细胞.
- 组合疗法抑制了谷氨介导的解毒和增加了氧化应激.
- 谷氨酸S转移酶卡帕1 (GSTK1) 被确定为放射敏感性的关键调节剂.
结论:
- 对于CCK2R阳性恶性瘤,DOTA-CCK2R-二次体在体内具有出色的稳定性,瘤保留性和成像性能.
- 与mTOR抑制的结合提供了一个协同策略,使瘤对放射治疗敏感.
- 这种方法对治疗耐火性CCK2R阳性癌症具有前途.
更多相关视频
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
15:04Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
相关概念视频
Targeted Cancer Therapies
There are several types of targeted therapies against...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
Mitogens and the Cell Cycle
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Inhibition of Cdk Activity
