Khan Syamantak, Zhong Xiaoxu, Das Neeladrisingha, Yu Jung Ho, Natarajan Arutselvan, Anders David, Pratx Guillem
Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
Department of Radiology, Stanford University, Stanford, CA, USA.
Eur J Nucl Med Mol Imaging. 2025 Apr;52(5):1778-1790. doi: 10.1007/s00259-024-07027-8. Epub 2024 Dec 27.
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.
We developed a Langmuir adsorption model that accurately describes the process of labeling mesoporous silica nanoparticles (MSNP) with Ga. 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 Ga 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.
We found that highly porous mesoporous nanoparticles (d = 100 nm) with MCM-41 pore structures can achieve radiolabeling efficiency > 30 GBq/mg using Ga, without the need for any chelator. These Ga conjugated particles showed strong serum stability in vitro. In mice, the Ga-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 Ga-MSNP-labeled cells allowed PET/CT tracking of these cells in various organs in mice.
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.
纳米颗粒是用于携带造影剂穿过细胞膜的高效载体，能够通过正电子发射断层扫描（PET）在体内对单个细胞进行超灵敏追踪。然而，在将这种方法可靠地应用于常规临床之前，必须对其进行全面的表征和了解。
我们开发了一种朗缪尔吸附模型，该模型能准确描述用镓标记介孔二氧化硅纳米颗粒（MSNP）的过程。通过将该模型拟合到实验数据，我们比较了三种不同纳米颗粒系统的结合效率。然后，我们选择了对镓具有最高亲和力的MSNP来研究其在癌细胞中的摄取和流出动力学。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性标记的有效性。
我们发现具有MCM - 41孔结构的高度多孔介孔纳米颗粒（直径 = 100 nm）使用镓可实现> 30 GBq/mg的放射性标记效率，且无需任何螯合剂。这些镓共轭颗粒在体外表现出很强的血清稳定性。在小鼠体内，镓 - MSNP主要积聚在肝脏中，具有高信噪比且无膀胱信号，表明标记的纳米颗粒在体内具有出色的稳定性。此外，共聚焦成像、流式细胞术分析和伽马计数证实，这些MSNP被B16F10和MDA - MB - 231癌细胞有效摄取。最后，心内注射< 100个镓 - MSNP标记的细胞可通过PET/CT在小鼠的各个器官中追踪这些细胞。
我们对MSNP介导的直接细胞放射性标记的关键参数进行了表征，以改善将这些纳米颗粒用作高灵敏度临床前PET成像的细胞标记物的应用。
