title: Multimodal molecular imaging system for pathway-specific reporter gene expression.
abstract: Preclinical imaging modalities represent an essential tool to develop a modern and translational biomedical research. To date, Optical Imaging (OI) and Magnetic Resonance Imaging (MRI) are used principally in separate studies for molecular imaging studies. We decided to combine OI and MRI together through the development of a lentiviral vector to monitor the Wnt pathway response to Lithium Chloride (LiCl) treatment. The construct was stably infected in glioblastoma cells and, after intracranial transplantation in mice, serial MRI and OI imaging sessions were performed to detect human ferritin heavy chain protein (hFTH) and firefly luciferase enzyme (FLuc) respectively. The system allowed also ex vivo analysis using a constitutive fluorescence protein expression. In mice, LiCl administration has shown significantly increment of luminescence signal and a lower signal of T2 values (P<0.05), recorded noninvasively with OI and a 7 Tesla MRI scanner. This study indicates that OI and MRI can be performed in a single in vivo experiment, providing an in vivo proof-of-concept for drug discovery projects in preclinical phase.
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy. Electronic address: mri@aol.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Massai
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Diamanti
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fiengo
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: De Rosa
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Magrini
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Magnoni
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Chellini
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Coniglio
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Diodato
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pilli
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Nicola Pasquale
authors.initials: NP
authors.lastname: Caradonna
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sardone
authors.affiliation: Noxamet Ltd., Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Monti
authors.affiliation: Noxamet Ltd., Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Roggeri
authors.affiliation: Laboratory of Medical Science, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.affiliation: Laboratory of Medical Science, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Recchia
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tunici
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Valensin
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Scali
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pollio
authors.affiliation: Siena Biotech Medicine Research Centre, Siena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Porcari
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics*; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D049409:Luciferases, Firefly / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008819:Mice, Nude; D057054:Molecular Imaging; D061848:Optical Imaging; D060449:Wnt Signaling Pathway
chemical_list: D001052:Apoferritins; D049409:Luciferases, Firefly; D018021:Lithium Chloride
keywords: BLI; MRI; Molecular Imaging; Multimodal imaging; Reporter gene