Fe(II)-Targeted PET/19F MRI Dual-Modal Molecular Imaging Probe for Early Evaluation of Anticancer Drug-Induced Acute Kidney Injury,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Fe(II)-Targeted PET/19F MRI Dual-Modal Molecular Imaging Probe for Early Evaluation of Anticancer Drug-Induced Acute Kidney Injury
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2023-09-15 , DOI: 10.1021/acs.molpharmaceut.3c00531
Sureya Nijiati ₁ , Fantian Zeng ₁ , Cuicui Zuo ₂ , Qianyu Zhang ₁ , Chao Du ₁ , Changrong Shi ₁ , Jinhao Gao ₂ , Zijian Zhou ₁

Affiliation

Ferroptosis, an iron-dependent regulated cell death, has been emerging as an early mechanism in anticancer drug-induced acute kidney injury (AKI) that may benefit therapeutic intervention. However, the lack of molecular imaging methods for in vivo detection of ferroptosis restricts the early diagnosis of anticancer drug-induced AKI. Herein, we developed a PET/¹⁹F MRI dual-modal imaging probe for the monitoring of ferroptosis in AKI by chemically conjugating the Fe(II)-sensitive artemisinin (Art) motif and macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the CF₃-modified polyhedral oligomeric silsesquioxane (POSS) clusters, denoted as the PAD probe. The PAD probe could be converted into PA*D in the presence of Fe(II) ions and subsequently be intercepted by biological macromolecules nearby, thereby enhancing the retention effect in ferroptotic cells and tissues. After labeling with ⁶⁸Ga isotopes, the ⁶⁸Ga-labeled PAD probe in cisplatin (CDDP)-induced AKI mice displayed a significantly higher renal uptake level than that in normal mice. Moreover, the PAD probe with a precise chemical structure, relatively high ¹⁹F content, and single ¹⁹F resonance frequency allowed for interference-free and high-performance¹⁹F MRI that could detect the onset of CDDP-induced AKI at least 24 h earlier than the typical clinical/preclinical assays. Our study provides a robust dual-modal molecular imaging tool for the early diagnosis and mechanistic investigation of various ferroptosis-related diseases.

中文翻译：

Fe(II) 靶向 PET/19F MRI 双模态分子成像探针用于抗癌药物引起的急性肾损伤的早期评估

铁死亡是一种铁依赖性调节细胞死亡，已成为抗癌药物引起的急性肾损伤（AKI）的早期机制，可能有利于治疗干预。然而，缺乏体内检测铁死亡的分子影像方法限制了抗癌药物引起的 AKI 的早期诊断。在此，我们开发了一种 PET/ ¹⁹ F MRI 双模态成像探针，通过化学结合 Fe(II) 敏感青蒿素 (Art) 基序和大环配体 1,4,7,10-四氮杂环十二烷-来监测 AKI 中的铁死亡。 1,4,7,10-四乙酸（DOTA）到CF ₃修饰的多面体低聚倍半硅氧烷（POSS）簇，表示为PAD探针。PAD探针在Fe(II)离子存在下可以转化为PA*D，随后被附近的生物大分子拦截，从而增强在铁死亡细胞和组织中的保留效果。用⁶⁸ Ga 同位素标记后，⁶⁸ Ga 标记的 PAD 探针在顺铂 (CDDP) 诱导的 AKI 小鼠中表现出明显高于正常小鼠的肾脏摄取水平。此外，PAD探针具有精确的化学结构、相对较高的¹⁹ F含量和单一的¹⁹ F共振频率，可以实现无干扰的高性能¹⁹ F MRI，可以提前至少24小时检测CDDP诱导的AKI的发作比典型的临床/临床前测定。我们的研究为各种铁死亡相关疾病的早期诊断和机制研究提供了强大的双模态分子成像工具。

更新日期：2023-09-15

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南