<br>通过 [89Zr]Zr(oxinate)4 直接放射性标记对小细胞外囊泡进行 PET 成像,Bioconjugate Chemistry

当前位置： X-MOL 学术 › Bioconjugate Chem. › 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.)

通过 [89Zr]Zr(oxinate)4 直接放射性标记对小细胞外囊泡进行 PET 成像
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2022-02-28 , DOI: 10.1021/acs.bioconjchem.1c00597
Azalea A Khan ₁ , Francis Man _{1,

2} , Farid N Faruqu ₂ , Jana Kim ₁ , Fahad Al-Salemee ₁ , Amaia Carrascal-Miniño ₁ , Alessia Volpe ₁ , Revadee Liam-Or ₂ , Paul Simpson ₃ , Gilbert O Fruhwirth ₁ , Khuloud T Al-Jamal ₂ , Rafael T M de Rosales ₁

Affiliation

外泌体或小细胞外囊泡（sEV）因其作为药物输送系统和疾病生物标志物的潜力而日益受到关注。因此，使用成像技术了解它们的体内生物分布非常重要，这种技术可以在整个身体水平上进行随时间的跟踪。正电子发射断层扫描 (PET) 可以对动物和人类的放射性标记化合物进行短期和长期全身跟踪，并且与其他核成像技术相比具有出色的量化特性。在本报告中，我们探索了使用[ ⁸⁹ Zr]Zr(oxinate) ₄ （一种细胞和脂质体放射性示踪剂）对几种类型的 sEV 进行直接和腔内放射性标记，实现了高放射性标记产率。放射合成和放射标记方案针对 sEV 标记进行了优化，避免了 sEV 损伤，如使用多种表征（冷冻电镜、纳米颗粒跟踪分析、斑点印迹和流式细胞术）和体外技术所证明的那样。在健康小鼠模型中使用胰腺癌 sEV (PANC1)，我们发现可以使用 PET 成像在体内追踪^{89 个}Zr 标记的 sEV 至少长达 24 小时。我们还报告了完整 sEV 与故意热损伤 sEV 相比的差异生物分布，后者的脾脏摄取显着减少。因此，我们得出结论，使用这种方法的^{89 个}Zr 标记的 sEV 可以可靠地用于体内PET 跟踪，从而可以有效地探索它们作为药物输送系统的潜力。

"点击查看英文标题和摘要"

PET Imaging of Small Extracellular Vesicles via [89Zr]Zr(oxinate)4 Direct Radiolabeling

Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand their in vivo biodistribution using imaging techniques that allow tracking over time and at the whole-body level. Positron emission tomography (PET) allows short- and long-term whole-body tracking of radiolabeled compounds in both animals and humans and with excellent quantification properties compared to other nuclear imaging techniques. In this report, we explored the use of [⁸⁹Zr]Zr(oxinate)₄ (a cell and liposome radiotracer) for direct and intraluminal radiolabeling of several types of sEVs, achieving high radiolabeling yields. The radiosynthesis and radiolabeling protocols were optimized for sEV labeling, avoiding sEV damage, as demonstrated using several characterizations (cryoEM, nanoparticle tracking analysis, dot blot, and flow cytometry) and in vitro techniques. Using pancreatic cancer sEVs (PANC1) in a healthy mouse model, we showed that it is possible to track ⁸⁹Zr-labeled sEVs in vivo using PET imaging for at least up to 24 h. We also report differential biodistribution of intact sEVs compared to intentionally heat-damaged sEVs, with significantly reduced spleen uptake for the latter. Therefore, we conclude that ⁸⁹Zr-labeled sEVs using this method can reliably be used for in vivo PET tracking and thus allow efficient exploration of their potential as drug delivery systems.

更新日期：2022-02-28

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南