title: Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors.
abstract: The development of in vivo imaging protocols to reliably track transplanted cells or to report on gene expression is critical for treatment monitoring in (pre)clinical cell and gene therapy protocols. Therefore, we evaluated the potential of lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) to express the magnetic resonance imaging (MRI) reporter gene ferritin in the rodent brain. First, we compared the induction of background MRI contrast for both vector systems in immune-deficient and immune-competent mice. LV injection resulted in hypointense (that is, dark) changes of T(2)/T(2)(*) (spin-spin relaxation time)-weighted MRI contrast at the injection site, which can be partially explained by an inflammatory response against the vector injection. In contrast to LVs, AAV injection resulted in reduced background contrast. Moreover, AAV-mediated ferritin overexpression resulted in significantly enhanced contrast to background on T(2)(*)-weighted MRI. Although sensitivity associated with the ferritin reporter remains modest, AAVs seem to be the most promising vector system for in vivo MRI reporter gene imaging.
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Vande Velde
authors.forename: J R
authors.initials: JR
authors.lastname: Rangarajan
authors.forename: J
authors.initials: J
authors.lastname: Toelen
authors.forename: T
authors.initials: T
authors.lastname: Dresselaers
authors.forename: A
authors.initials: A
authors.lastname: Ibrahimi
authors.forename: O
authors.initials: O
authors.lastname: Krylychkina
authors.forename: R
authors.initials: R
authors.lastname: Vreys
authors.forename: A
authors.initials: A
authors.lastname: Van der Linden
authors.forename: F
authors.initials: F
authors.lastname: Maes
authors.forename: Z
authors.initials: Z
authors.lastname: Debyser
authors.forename: U
authors.initials: U
authors.lastname: Himmelreich
authors.forename: V
authors.initials: V
authors.lastname: Baekelandt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D051379:Mice; D057054:Molecular Imaging; D012680:Sensitivity and Specificity
chemical_list: D005293:Ferritins