title: Immobilizing reporters for molecular imaging of the extracellular microenvironment in living animals.
abstract: We report here an immobilization strategy using a collagen binding protein to deliver and confine synthetic reporters to the extracellular microenvironment in vivo for noninvasively imaging the activity of targets in the microenvironment. We show that the immobilization of reporters on collagens in the local microenvironment is highly efficient and physiologically stable for repetitive, long-term imaging. By using this strategy we successfully developed an immobilized bioluminescent activatable reporter and a dual-modality reporter to map and quantitatively image the activity of extracellular matrix metalloproteinases (MMP) in tumor-bearing mice. The inhibition of MMP activity by chemical inhibitor was also demonstrated in living subjects. We further demonstrated the general applicability of this immobilization strategy by imaging MMP activity at the inflammation site in a mouse model. Our results show that the in vivo immobilization of reporters can be used as a general strategy for probing the local extracellular microenvironment.
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology & Bio-X Program, Stanford University, California 94035-5484, United States.
authors.forename: Zuyong
authors.initials: Z
authors.lastname: Xia
authors.forename: Yun
authors.initials: Y
authors.lastname: Xing
authors.forename: Jongho
authors.initials: J
authors.lastname: Jeon
authors.forename: Young-Pil
authors.initials: YP
authors.lastname: Kim
authors.forename: Jessica
authors.initials: J
authors.lastname: Gall
authors.forename: Anca
authors.initials: A
authors.lastname: Dragulescu-Andrasi
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D049408:Luminescent Agents / Q000032:analysis / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D059016:Tumor Microenvironment
chemical_list: D049408:Luminescent Agents; D003094:Collagen; D020782:Matrix Metalloproteinases