title: Multimodal imaging of neural progenitor cell fate in rodents.
abstract: 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.
authors.affiliation: Laboratory for Gene Therapy and Molecular Imagin, Max=Planck Institute for Neurological Research, Cologne, Germany.
authors.forename: Yannic
authors.initials: Y
authors.lastname: Waerzeggers
authors.forename: Markus
authors.initials: M
authors.lastname: Klein
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Miletic
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Li
authors.forename: Parisa
authors.initials: P
authors.lastname: Monfared
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.forename: Heinrich Hubert
authors.initials: HH
authors.lastname: Coenen
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.forename: Andreas Hans
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: 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
chemical_list: D008164:Luminescent Proteins; D014764:Viral Proteins; D049409:Luciferases, Firefly; D013937:Thymidine Kinase