99mTc-Based Imaging of Transplanted Neural Stem Cells and Progenitor Cells

Abstract

Cell therapy for neurologic disorders will benefit significantly from progress in methods of noninvasively imaging cell transplants. The success of current cell therapy has varied, in part because of differences in cell sources, differences in transplantation procedures, and lack of understanding of cell fate after transplantation. Standardization of transplantation procedures will progress with noninvasive imaging. In turn, in vivo imaging will enhance our understanding of neural transplant biology and improve therapeutic outcomes. The goal of this study was to determine the effect of a 99m Tc-based probe on neural stem and progenitor cell transplants and validate the SPECT images of the transplanted cells. Methods: We previously developed a method to label neural stem and progenitor cells with 99m Tc to visualize these cells in the brain with SPECT. The cells were initially labeled with a permeation peptide carrying a chelate for 99m Tc. The proliferation and differentiation characteristics of the labeled cells were studied in tissue culture. In parallel experiments, the labeled cells were stereotactically injected into the rat brain, and the site of transplantation was verified with histochemistry and phosphorimaging. Results: The accuracy of the transplant location obtained by SPECT was confirmed by comparison with phosphorimages and histologic sections of the brain. The labeling did, however, decrease the proliferative capacity of the neural stem and progenitor cells. Conclusion: The labeling technique described here can be used to standardize the location of cell transplants in the brain and quantify the number of transplanted cells. However, a 99m Tc-based probe can decrease the cellular proliferation of neural progenitor cells.

Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging

“…Radionuclide imaging techniques are highly quantitative in nature and therefore several groups have directly labeled NSCs and MSCs with either 18 F-FDG [ 142 ], 99m Tc-HMPAO [ 143 – 146 ], or 111 In-oxine [ 147 – 149 ]. After labeling with radionuclides no differences in viability or differentiation capacity were shown; no ultrastructural changes were shown either [ 111 , 142 – 144 , 147 – 149 ].…”

“…18 F-FDG did also not induce metabolic changes while 111 In-oxine reduced metabolic activity and motility of the cells [ 148 ]. A reduced proliferation rate was also seen in 99m Tc-labeled NSCs, probably because of DNA damage induced by Auger electrons [ 146 ].…”

Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

“…and, therefore, can assess the biodistribution of transplanted cells straight after injection [39–41]. In one study of Gleave et al [42], they developed a method to label neural stem and progenitor cells with 99m Tc to visualize these cells in the brain with SPECT. The cells were initially labeled with a permeation peptide carrying a chelator for 99m Tc.…”

“…The labeling technique described here can be used to standardize the location of cell transplants in the brain and quantify the number of transplanted cells. This information will be useful in standardizing cellular transplantations to achieve reproducible outcomes [42]. Labeling of cells with exogenous nonspecific nuclear imaging agents is easily achievable.…”

Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes

“…However, in one study of Gleave et al, labeling neural stem and progenitor cells with 99 mTc decreased the proliferative capacity of those cells. Clinical studies using 99 mTc-HMPAO tracking stem cells are mainly involve in those with chronic ischemic cardiomyopathy or myocardial infarction at present [ 30 ]. A best example of radiotracer used in central nervous system is 2-deoxy-2-[ 18 F]fluoro-D-glucose, or 18 F-FDG (half-life: 109 min), which is transported into cells via the GLUT transporter family.…”