Klinische Neurophysiologie 2012; 43 - V090
DOI: 10.1055/s-0032-1301486

Non-invasive imaging of endogenous neural stem cell mobilization in vivo using Positron Emission Tomography

MA Rueger 1, H Backes 2, M Walberer 1, B Neumaier 2, R Ullrich 2, B Emig 1, ML Simard 1, GR Fink 1, M Hoehn 2, R Graf 2, M Schroeter 1
  • 1Klinik für Neurologie, Uniklinik Köln, Köln
  • 2Max-Planck-Institut für Neurologische Forschung, Köln

Neural stem cells reside in two major niches in the adult brain, i.e. the subventricular zone (SVZ) and the dentate gyrus of the hippocampus. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain’s own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche is required. We established a non-invasive imaging assay using Positron Emission Tomography (PET) and the radiotracer 3’-deoxy–3’-[18F]fluoro-L-thymidine ([18F]FLT) that enables imaging and measuring of proliferation, in order to non-invasively detect endogenous neural stem cells in the normal and diseased adult rat brain in vivo. This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [18F]FLT-binding in the SVZ and the hippocampus. Focal cerebral ischemia and subsequent damage of the blood-brain barrier did not interfere with the capability of [18F]FLT-PET to visualize neural stem cell mobilization. Moreover, [18F]FLT-PET allowed for an in vivo quantification of increased neural stem cell mobilization caused by pharmacological stimulation or by focal cerebral ischemia. We suggest that non-invasive, longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible, and that [18F]FLT-PET can be used to monitor the effects of drugs aimed at expanding the neural stem cell niche.

Literatur: Rueger MA, Backes H, Walberer M, Neumaier B, Ullrich R, Simard ML, Emig B, Fink GR, Hoehn M, Graf R, Schroeter M (2010). Non-invasive imaging of endogenous neural stem cell mobilization in vivo using Positron Emission Tomography. J Neurosci; 30(18):6454-6460.