Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma

Shih Hsun Cheng, Dou Yu, Hsiu Ming Tsai, Ramin A. Morshed, Deepak Kanojia, Leu Wei Lo, Lara Leoni, Yureve Govind, Lingjiao Zhang, Karen S. Aboody, MacIej S. Lesniak, Chin Tu Chen, Irina V. Balyasnikova*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Neural Stem Cells
Glioblastoma
Single-Photon Emission-Computed Tomography
Nanoparticles
Silicon Dioxide
Glioma
Histology
Brain
Cell Tracking
Technology
Injections
Nanostructures
Feasibility Studies
Heterografts
Confocal Microscopy
Therapeutics
Immunohistochemistry

Keywords

  • Cell tracking
  • Glioma
  • Nanoparticle
  • Neural stem cells
  • SPECT

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Cheng, Shih Hsun ; Yu, Dou ; Tsai, Hsiu Ming ; Morshed, Ramin A. ; Kanojia, Deepak ; Lo, Leu Wei ; Leoni, Lara ; Govind, Yureve ; Zhang, Lingjiao ; Aboody, Karen S. ; Lesniak, MacIej S. ; Chen, Chin Tu ; Balyasnikova, Irina V. / Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 2. pp. 279-284.
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title = "Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma",
abstract = "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.",
keywords = "Cell tracking, Glioma, Nanoparticle, Neural stem cells, SPECT",
author = "Cheng, {Shih Hsun} and Dou Yu and Tsai, {Hsiu Ming} and Morshed, {Ramin A.} and Deepak Kanojia and Lo, {Leu Wei} and Lara Leoni and Yureve Govind and Lingjiao Zhang and Aboody, {Karen S.} and Lesniak, {MacIej S.} and Chen, {Chin Tu} and Balyasnikova, {Irina V.}",
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Cheng, SH, Yu, D, Tsai, HM, Morshed, RA, Kanojia, D, Lo, LW, Leoni, L, Govind, Y, Zhang, L, Aboody, KS, Lesniak, MS, Chen, CT & Balyasnikova, IV 2016, 'Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma', Journal of Nuclear Medicine, vol. 57, no. 2, pp. 279-284. https://doi.org/10.2967/jnumed.115.163006

Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma. / Cheng, Shih Hsun; Yu, Dou; Tsai, Hsiu Ming; Morshed, Ramin A.; Kanojia, Deepak; Lo, Leu Wei; Leoni, Lara; Govind, Yureve; Zhang, Lingjiao; Aboody, Karen S.; Lesniak, MacIej S.; Chen, Chin Tu; Balyasnikova, Irina V.

In: Journal of Nuclear Medicine, Vol. 57, No. 2, 01.02.2016, p. 279-284.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma

AU - Cheng, Shih Hsun

AU - Yu, Dou

AU - Tsai, Hsiu Ming

AU - Morshed, Ramin A.

AU - Kanojia, Deepak

AU - Lo, Leu Wei

AU - Leoni, Lara

AU - Govind, Yureve

AU - Zhang, Lingjiao

AU - Aboody, Karen S.

AU - Lesniak, MacIej S.

AU - Chen, Chin Tu

AU - Balyasnikova, Irina V.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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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KW - Glioma

KW - Nanoparticle

KW - Neural stem cells

KW - SPECT

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