[F]FDG Labeling of Neural Stem Cells for in Vivo Cell Tracking with Positron Emission Tomography: Inhibition of Tracer Release by Phloretin

Abstract

The introduction of neural stem cells into the brain has promising therapeutic potential for the treatment of neurodegenerative diseases. To monitor the cellular replacement therapy, that is, to determine stem cell migration, survival, and differentiation, in vivo tracking methods are needed. Ideally, these tracking methods are noninvasive. Noninvasive tracking methods that have been successfully used for the visualization of blood-derived progenitor cells include magnetic resonance imaging and radionuclide imaging using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The SPECT tracer In-111-oxine is suitable for stem cell labeling, but for studies in small animals, the higher sensitivity and facile quantification that can be obtained with PET are preferred. Here the potential of 2′-[ 18 F]fluoro-2′-deoxy-D-glucose ([ 18 F]-FDG), a PET tracer, for tracking of neural stem cell (NSCs) trafficking toward an inflammation site was investigated. [ 18 F]-FDG turns out to be a poor radiopharmaceutical to label NSCs owing to the low labeling efficiency and substantial release of radioactivity from these cells. Efflux of [ 18 F]-FDG from NSCs can be effectively reduced by phloretin in vitro, but inhibition of tracer release is insufficient in vivo for accurate monitoring of stem cell trafficking.