Efficient Nanoparticle-Mediated Radiolabeling of Cells for in Vivo PET Tracking
Presentations
SU-F-202-1 (Sunday, 7/10/2022) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]
Room 202
Purpose: The ability to track cells in vivo offers new opportunities for studying cancer metastasis and cancer immunotherapy. Our previous study shows PET is able to track the movements of individual radiolabeled cells with high resolution only using a few becquerels (Bq) of radioactivity. However, cellular efflux causes gradual degradation of radioactive signals from the cells, creating a serious bottleneck for advancing this technology and tracking multiple cells at a time. To mitigate this challenge, a much higher radiolabeling and retention efficiency is warranted.
Methods: Here we optimize 3 steps of the radiolabeling protocol of B16F10 mouse melanoma cells with gallium-68 (68Ga). 1) We screened nanoparticles of various sizes and porosity. 2) To maximize cell uptake and minimize efflux, the cellular trafficking of 68Ga-MSN was investigated. 3) Finally, we developed a cell sorting strategy to characterize the distribution of radiolabeled cells and selectively sort cells with the highest 68Ga-MSN uptake using an automated single-cell dispenser.
Results: Mesoporous silica nanospheres (MSN) with 100 nm diameter and a hexagonal MCM-41 pore structure have the highest binding affinity towards 68Ga, possibly due to the excellent porosity and a high surface to volume ratio. Moreover, a positively charged lipid coating on MSN improves the cellular retention of 68Ga-MSN ~4 fold in a serum-free media, while a serum-mediated protein corona reduces it slightly. Finally, with 68Ga-MSN-actuated cell sorting, we enriched highly radiolabeled cells and isolated single cells with a final labeling efficiency > 100 Bq.
Conclusion: We developed a new strategy to achieve a very high radiolabeling efficiency of B16F10 cells. This labeling method is chelator-free, rapid, non-specific, and therefore can be effectively deployed in any other mammalian cells. Thanks to the excellent biocompatibility of MSN, our method paves the way for tracking circulating tumor cells and immune cells in human patients.
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