title: A novel adenoviral vector labeled with superparamagnetic iron oxide nanoparticles for real-time tracking of viral delivery.
abstract: In vivo tracking of gene therapy vectors challenges the investigation and improvement of biodistribution of these agents in the brain, a key feature for their targeting of infiltrative malignant gliomas. The glioma-targeting Ad5/3-cRGD gene therapy vector was covalently bound to super-paramagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPION) to monitor its distribution by MRI. Transduction of labeled and unlabeled vectors was assessed on the U87 glioma cell line and normal human astrocytes (NHA), and was higher in U87 compared to NHA, but was similar between labeled and unlabeled virus. An in vivo study was performed by intracranial subcortical injection of labeled-Ad5/3-cRGD particles into a pig brain. The labeled vector appeared in vivo as a T2-weighted hyperintensity and a T2-gradient echo signal at the injection site, persisting up to 72 hours post-injection. We describe a glioma-targeting vector that is labeled with SPION, thereby allowing for MRI detection with no change in transduction capability.
authors.affiliation: Gabriele Bartoli Brain Tumor Laboratory, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yun
authors.forename: Adam M
authors.initials: AM
authors.lastname: Sonabend
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Ulasov
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Elena A
authors.initials: EA
authors.lastname: Rozhkova
authors.forename: Valentyn
authors.initials: V
authors.lastname: Novosad
authors.forename: Stephen
authors.initials: S
authors.lastname: Dashnaw
authors.forename: Truman
authors.initials: T
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003911:Dextrans / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism*; D005822:Genetic Vectors / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D053758:Nanoparticles; D051381:Rats; D012235:Rhodamines / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D003911:Dextrans; D005290:Ferric Compounds; C067661:Fluoro-Ruby; D058185:Magnetite Nanoparticles; D012235:Rhodamines; D049452:Green Fluorescent Proteins; C000499:ferric oxide; C065507:ferumoxides