Purpose

Nanoparticles are highly efficient vectors for ferrying contrast agents across cell membranes, enabling ultra-sensitive in vivo tracking of single cells with positron emission tomography (PET). However, this approach must be fully characterized and understood before it can be reliably implemented for routine applications.

Methods

We developed a Langmuir adsorption model that accurately describes the process of labeling mesoporous silica nanoparticles (MSNP) with ⁶⁸Ga. We compared the binding efficiency of three different nanoparticle systems by fitting the model to experimental data. We then chose the MSNP with the highest affinity for ⁶⁸Ga to study uptake and efflux kinetics in cancer cells. After intracardiac injection of 50–100 cells in mice, PET imaging was performed to test the effectiveness of cellular radiolabeling.

Results

We found that highly porous mesoporous nanoparticles (d = 100 nm) with MCM-41 pore structures can achieve radiolabeling efficiency > 30 GBq/mg using ⁶⁸Ga, without the need for any chelator. These ⁶⁸Ga conjugated particles showed strong serum stability in vitro. In mice, the ⁶⁸Ga-MSNPs predominantly accumulated in the liver with a high signal-to-background ratio and no bladder signal, indicating excellent stability of the labeled nanoparticles in vivo. Additionally, these MSNPs were efficiently taken up by B16F10 and MDA-MB-231 cancer cells, as confirmed by confocal imaging, flow cytometry analysis, and gamma counting. Finally, cardiac injection of < 100 ⁶⁸Ga-MSNP-labeled cells allowed PET/CT tracking of these cells in various organs in mice.

Conclusion

We characterized the critical parameters of MSNP-mediated direct cellular radiolabeling to improve the use of these nanoparticles as cellular labels for highly sensitive preclinical PET imaging.

中文翻译：

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用于单细胞 PET 成像的介孔二氧化硅纳米颗粒的高效放射性标记

 目的

纳米颗粒是跨细胞膜运输造影剂的高效载体，可通过正电子发射断层扫描 （PET） 对单细胞进行超灵敏的体内追踪。但是，必须先充分表征和理解这种方法，然后才能可靠地将其用于常规应用。

 方法

我们开发了一个 Langmuir 吸附模型，该模型准确描述了用 ⁶⁸Ga标记介孔二氧化硅纳米颗粒 （MSNP） 的过程。我们通过将模型与实验数据拟合来比较三种不同纳米颗粒系统的结合效率。然后，我们选择对 ⁶⁸Ga 具有最高亲和力的 MSNP 来研究癌细胞中的摄取和外排动力学。在小鼠心内注射 50-100 个细胞后，进行 PET 成像以测试细胞放射标记的有效性。

 结果

我们发现具有 MCM-41 孔结构的高多孔介孔纳米颗粒 （d = 100 nm） 可以使用 ⁶⁸Ga实现放射性标记效率 > 30 GBq/mg，而无需任何螯合剂。这些 ⁶⁸Ga 偶联颗粒在体外表现出很强的血清稳定性。在小鼠中，⁶⁸个 Ga-MSNPs 主要在肝脏中积累，信噪比高，无膀胱信号，表明标记的纳米颗粒在体内具有出色的稳定性。此外，这些 MSNP 被 B16F10 和 MDA-MB-231 癌细胞有效摄取，共聚焦成像、流式细胞术分析和 γ 计数证实了这一点。最后，心脏注射 < 100 ⁶⁸Ga-MSNP 标记的细胞允许对小鼠各个器官中的这些细胞进行 PET/CT 跟踪。

 结论

我们表征了 MSNP 介导的直接细胞放射标记的关键参数，以改善这些纳米颗粒作为高灵敏度临床前 PET 成像的细胞标记的使用。