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.
Keywords: Cell tracking; Gallium-68; Mesoporous silica; Nanoparticle; PET imaging.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.