Article

Immobilizing reporters for molecular imaging of the extracellular microenvironment in living animals.

Molecular Imaging Program at Stanford, Department of Radiology & Bio-X Program, Stanford University, California 94035-5484, United States.
ACS Chemical Biology (impact factor: 6.45). 08/2011; 6(10):1117-26. DOI:10.1021/cb200135e pp.1117-26
Source: PubMed

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.

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Keywords

chemical inhibitor
 
collagen binding protein
 
confine synthetic reporters
 
extracellular matrix metalloproteinases
 
extracellular microenvironment
 
general applicability
 
general strategy
 
imaging MMP activity
 
immobilization strategy
 
immobilized bioluminescent activatable reporter
 
inflammation site
 
local extracellular microenvironment
 
local microenvironment
 
long-term imaging
 
MMP activity
 
noninvasively imaging
 
physiologically stable
 
quantitatively image
 
tumor-bearing mice
 
vivo immobilization
 

Zuyong Xia