Multimodal imaging of neural progenitor cell fate in rodents.
For clinical application of stem cell-based therapies, noninvasive detection of applied stem cells is of high importance. We report on the feasibility of detecting implanted neural progenitor cells (NPCs) noninvasively and follow their fate and functional status by sequential multimodal molecular imaging and reporter gene technology. We investigated C17.2 cells stably expressing herpes simplex virus type 1-thymidine kinase (HSV-1-tk) and green fluorescent protein (gfp) (C17.2-tkIRESgfp = C17.2-TIG) or HSV-1-tk, gfp, and firefly luciferase (luc) (C17.2-lucIREStkgfp = C17.2-LITG) and determined the detection sensitivity of positron emission tomography (PET) and bioluminescence imaging (BLI) for these cells in culture and in vivo in subcutaneous and intracranial glioma models. In addition, PET and BLI were used to further investigate and follow the fate of implanted C17.2-LITG cells in an intracranial glioma model. We show that both imaging modalities are sensitive in detecting reporter gene expressing NPCs; however, PET, by the use of 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG), detects NPCs only at sites of disrupted blood-brain barrier. Furthermore, both imaging modalities can be used to detect stem cell fate and migration and indicate excessive proliferation and aberrant migration. In conclusion, multimodal imaging can be used for longitudinal noninvasive monitoring of grafted NPCs in rodents.
Waerzeggers
Yannic
Y
Laboratory for Gene Therapy and Molecular Imagin, Max=Planck Institute for Neurological Research, Cologne, Germany.
Klein
Markus
M
Miletic
Hrvoje
H
Himmelreich
Uwe
U
Li
Hongfeng
H
Monfared
Parisa
P
Herrlinger
Ulrich
U
Hoehn
Mathias
M
Coenen
Heinrich Hubert
HH
Weller
Michael
M
Winkeler
Alexandra
A
Jacobs
Andreas Hans
AH
D000818:Animals; D002460:Cell Line; D017930:Genes, Reporter; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D008164:Luminescent Proteins; D014764:Viral Proteins; D049409:Luciferases, Firefly; D013937:Thymidine Kinase