Correlative Spect Imaging Of Neural Stem/Progenitor Cell Transplants In A Rat Model Of Parkinson's Disease

Abstract

<p> Cell therapy for Parkinson's disease will greatly benefit from progress in methods aimed at visualizing the dopamine system and cell replacement techniques. Currently, cell therapy has been met with varied success, in part due to differences in cell sources, transplantation procedures, and our lack of understanding of cell fate post-transplantation. The standardization of transplantation procedures will enhance our ability to draw comparisons between studies and improve cell therapy outcomes. We developed a method to label neural stem/progenitor cells (NSPCs) with technetium-99m and then visualize the cells with single photon emission computed tomography (SPECT) subsequent to grafting in the brain. This labeling method permitted a high uptake of the tracer into the cells without causing damage to the DNA or altering cell viability. The labeling caused a significant decrease (75%) in the proliferative capacity of the SPCs and caused a trend towards an increase in neuronal differentiation. Using this technique paves the way to standardize the location of the transplant and quantify the number transplanted cells while increasing the production of neurons.</p> <p> Experiments were performed to visualize the dopamine system with [(123)I]altropane at pre-and post-transplant time points in the 6-0HDA rat model of Parkinson's disease. [(123)I]altropane binding correlated with the content of dopamine in the stria tum. However, [(123)I]altropane binding was not correlated with dopamine content in the substantia nigra and did not show a correlation with the amphetamine rotations. However, there was a significant correlation with the cylinder test and the postural instability test. When the data was assessed using linear regression, the r^2 value of the linear relationship was low indicating that [(123)I]altropane SPECT is not a good predictor of behavioural outcome due to a weak linear relationship. Our data indicates that [(123)I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. The results are discussed in relation to the use of [(123)I]altropane in comparison to other dopamine SPECT and PET agents. </p>