title: Single reporter for targeted multimodal in vivo imaging.
abstract: We have developed a multifaceted, highly specific reporter for multimodal in vivo imaging and applied it for detection of brain tumors. A metabolically biotinylated, membrane-bound form of Gaussia luciferase was synthesized, termed mbGluc-biotin. We engineered glioma cells to express this reporter and showed that brain tumor formation can be temporally imaged by bioluminescence following systemic administration of coelenterazine. Brain tumors expressing this reporter had high sensitivity for detection by magnetic resonance and fluorescence tomographic imaging upon injection of streptavidin conjugated to magnetic nanoparticles or fluorophore, respectively. Moreover, single photon emission computed tomography showed enhanced imaging of these tumors upon injection with streptavidin complexed to (111)In-DTPA-biotin. This work shows for the first time a single small reporter (∼40 kDa) which can be monitored with most available molecular imaging modalities and can be extended for single cell imaging using intravital microscopy, allowing real-time tracking of any cell expressing it in vivo.
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Boston, United States.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Niers
authors.forename: John W
authors.initials: JW
authors.lastname: Chen
authors.forename: Grant
authors.initials: G
authors.lastname: Lewandrowski
authors.forename: Mariam
authors.initials: M
authors.lastname: Kerami
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Garanger
authors.forename: Greg
authors.initials: G
authors.lastname: Wojtkiewicz
authors.forename: Peter
authors.initials: P
authors.lastname: Waterman
authors.forename: Edmund
authors.initials: E
authors.lastname: Keliher
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Bakhos A
authors.initials: BA
authors.lastname: Tannous
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000737:chemistry / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D059010:Single-Cell Analysis / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D001710:Biotin; D008156:Luciferases