案例信息
标题：Fe(II)靶向的PET/19F MRI双模态分子探针用于化疗药物引发的急性肾损伤的早期评估
【专业学位类别】公共卫生
【专业领域/方向】转化医学
【作者】周子健
【单位】bet体育365官网正规
【关键词】急性肾损伤;铁死亡;正电子发射断层扫描;磁共振成像;早期评估
【适用课程】转化医学选论
【案例摘要】
急性肾损伤（Acute kidney injury, AKI）是肿瘤患者使用化疗药物过程中引起的严重副作用之一，具有高的发病率和致死率。近期研究表明，对肾脏损伤进行早期干预可有效防止AKI病情的加重，但目前仍缺乏有效针对化疗药物引发AKI的诊断策略。铁死亡是一种调节性细胞死亡类型，主要特征为铁依赖的脂质过氧化物的积累为特征。研究发现多种化疗药物引发的AKI模型中，铁死亡抑制剂可有效缓解AKI的病情，说明铁死亡可能参与AKI发生发展过程。鉴于氧化还原活性的Fe(II) 是在铁死亡机制中的关键调节因子，靶向细胞内Fe(II)离子可能是化疗药物引发的AKI的一种有效的早期诊断策略。基于此本研究由青蒿素（Artemisinin, Art）的抗疟机制获得灵感，设计了一种Fe(II)响应性的 PET/19F MRI双模态成像探针POSS-Art-DOTA （PAD），通过靶向Fe(II)来早期评估顺铂（CDDP）诱导的AKI。通过解读该研究的关键环节，使学生掌握分子探针的合成和成像方法，学习实验方案的设计与实施，培养科研素养与思维。
Title:Fe(II)-targeted PET/19F MRI dual-modal molecular probe for early evaluation of anticancer drugs-induced AKI
Professional Degree Category: Master of Public Health
Specialized fields: Translational Medicine
Authors: Zijian Zhou
Affiliation: School of Public Health, Xiamen University
Key words: Acute kidney injury （AKI）; Ferroptosis; Positron emission tomography （PET）; Magnetic resonance imaging （MRI）; early evaluation
Abstract
The use of clinical anticancer drugs is one of the leading causes of acute kidney injury (AKI) cases. Recent studies have shown that timely renoprotective intervention could prevent AKI from progressing into more serious complications, yet there is still a lack of effective diagnosis strategy for anticancer drug-induced AKI. Ferroptosis is a newly recognized type of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. Pharmacological inhibitors of ferroptosis could be employed to alleviate the progression of AKI which have been demonstrated in multiple anticancer drug-induced AKI. It was suggested that ferroptosis is an early molecular event of AKI. Given that the redox-active Fe(II) plays a key role in the mechanism of ferroptosis, targeting intracellular Fe(II) ions may serve as a vivid chemical strategy for the early diagnosis of anticancer drug-induced AKI. Inspired by the mechanism of antimalarial artemisinin (Art), we designed a new PET/19F MRI dual-modal imaging probe named POSS-Art-DOTA (PAD) for early evaluation of cisplatin (CDDP)-induced AKI by targeting Fe(II). By interpreting the key links of this research, students can master the synthesis and imaging methods of molecular probes, learn the design and implementation of experimental programs, and cultivate scientific research literacy and thinking.
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【案例说明书】
