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中文摘要
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描述(申请人提供):将肿瘤的酸性细胞外空间碱化的治疗方法正在开发中,作为廉价的抗癌替代品,可以减少转移和恶性肿瘤。其中一种碱化疗法,口服碳酸氢盐,已被证明特别有效,最近已被FDA批准为临床癌症试验的研究新药。这种疗法的一个缺点是高剂量的碳酸氢盐会损害肾功能,因此优化碳酸氢盐的治疗非常重要。我们建议开发一类新的小分子磁共振造影剂,用于记录肿瘤组织的pH值,以监测和优化碱化治疗。这些工作将使用具有两个不同可交换质子的pH敏感的parCEST磁共振造影剂,可用于组织中的比例浓度独立的pH监测。(parCEST=顺磁化学交换饱和转移)。这一方法正在为含有造影剂的稀土元素(Ln(III))开发,但由于缺乏具有较大顺磁诱导质子位移的不同类型的可交换质子,因此存在问题。Morrow实验室的工作表明,铁(Fe(II))络合物可以发展成parCEST磁共振造影剂。与目前正在开发的Ln(III)配合物相比,Fe(II)配合物对CEST具有更尖锐和更高位移的质子共振。此外,铁的络合物可能更便宜,毒性也更小。我们将开发这些新的铁基试剂作为小分子显像剂和树枝状大分子来控制滞留和肿瘤摄取。这些药物将在小鼠乳腺肿瘤中进行测试。
英文摘要
DESCRIPTION (provided by applicant): Treatments that alkalinize the acidic extracellular space of tumors are under development as inexpensive anticancer alternatives that reduce metastasis and malignancy. One of these alkalinizing therapies, oral bicarbonate, has been shown to be particularly effective and has been recently approved by the FDA as an investigational new drug for clinical cancer trials. A drawback of this therapy is that high doss of bicarbonate impair kidney function, making it important to optimize bicarbonate treatments. We propose to develop a new class of small molecule MRI contrast agents for the registration of pH in tumor tissue to monitor and optimize alkalinizing treatments. These efforts will use pH sensitive paraCEST MRI contrast agents with two different exchangeable protons that can be used for ratiometric concentration independent pH monitoring in tissue. (paraCEST = paramagnetic chemical exchange saturation transfer). This approach is under development for lanthanide (Ln(III)) containing contrast agents, but is problematic because of the lack of different types of exchangeable protons with large paramagnetic induced proton shifts. Work in the Morrow laboratory has shown that iron (Fe(II)) complexes can be developed into paraCEST MRI contrast agents. Fe(II) complexes have sharper and more highly shifted proton resonances for CEST than the Ln(III) complexes currently under development. In addition, the iron complexes may be potentially be less expensive and less toxic. We will develop these new iron based agents both as small molecule imaging agents and as dendrimers to control retention and tumor uptake. These agents will be tested in mouse mammary tumors.
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Self-assembled iron(III) hosts for MRI-guided delivery of chemotherapeutics
Self-assembled iron(III) hosts for MRI-guided delivery of chemotherapeutics
Iron PARACEST MRI Contrast Agents for Monitoring Hyperthermia-based Therapy
Iron paraCEST MRI Contrast Agents for Monitoring Tumor Acidosis
国内基金
海外基金
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
  • 依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
    雷芬芳
  • 依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    --
  • 批准年份:
    2024
  • 负责人:
    万荣
  • 依托单位: