Dynamic In Vivo SPECT Imaging of Neural Stem Cells Functionalized with Radiolabeled Nanoparticles for Tracking of Glioblastoma

There is strong clinical interest in using neural stem cells (NSCs) as carriers for targeted delivery of therapeutics to glioblastoma. Multimodal dynamic in vivo imaging of NSC behaviors in the brain is necessary for developing such tailored therapies; however, such technology is lacking. Here we report a novel strategy for mesoporous silica nanoparticle (MSN)–facilitated NSC tracking in the brain via SPECT. Methods: ¹¹¹In was conjugated to MSNs, taking advantage of the large surface area of their unique porous feature. A series of nanomaterial characterization assays was performed to assess the modified MSN. Loading efficiency and viability of NSCs with ¹¹¹In-MSN complex were optimized. Radiolabeled NSCs were administered to glioma-bearing mice via either intracranial or systemic injection. SPECT imaging and bioluminescence imaging were performed daily up to 48 h after NSC injection. Histology and immunocytochemistry were used to confirm the findings. Results: ¹¹¹In-MSN complexes show minimal toxicity to NSCs and robust in vitro and in vivo stability. Phantom studies demonstrate feasibility of this platform for NSC imaging. Of significance, we discovered that decayed ¹¹¹In-MSN complexes exhibit strong fluorescent profiles in preloaded NSCs, allowing for ex vivo validation of the in vivo data. In vivo, SPECT visualizes actively migrating NSCs toward glioma xenografts in real time after both intracranial and systemic administrations. This is in agreement with bioluminescence live imaging, confocal microscopy, and histology. Conclusion: These advancements warrant further development and integration of this technology with MRI for multimodal noninvasive tracking of therapeutic NSCs toward various brain malignancies.

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