PT  - JOURNAL ARTICLE
AU  - Shih-Hsun Cheng
AU  - Dou Yu
AU  - Hsiu-Ming Tsai
AU  - Ramin A. Morshed
AU  - Deepak Kanojia
AU  - Leu-Wei Lo
AU  - Lara Leoni
AU  - Yureve Govind
AU  - Lingjiao Zhang
AU  - Karen S. Aboody
AU  - Maciej S. Lesniak
AU  - Chin-Tu Chen
AU  - Irina V. Balyasnikova
TI  - Dynamic In Vivo SPECT Imaging of Neural Stem Cells Functionalized with Radiolabeled Nanoparticles for Tracking of Glioblastoma
AID  - 10.2967/jnumed.115.163006
DP  - 2016 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 279--284
VI  - 57
IP  - 2
4099  - http://jnm.snmjournals.org/content/57/2/279.short
4100  - http://jnm.snmjournals.org/content/57/2/279.full
SO  - J Nucl Med2016 Feb 01; 57
AB  - 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.