Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.
OBJECTIVE
To develop an optical imaging method to determine the expression level of tumoral matrix metalloproteinase-2 (MMP-2) in vivo.


METHODS
An optical contrast agent was developed that was highly activatable by means of MMP-2-induced conversion. Signal characteristics of the probe were quantified ex vivo with a recombinant enzyme. Animal tumor models were established with MMP-2-positive (human fibrosarcoma cell line, n = 4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n = 4) tumor cell lines. Both tumors were implanted into nude mice and were optically imaged after intravenous administration of the MMP-2-sensitive probe.


RESULTS
The MMP-2-sensitive probe was activated by MMP-2 in vitro, producing up to an 850% increase in near-infrared fluorescent signal intensity. This activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors were easily identified as high-signal-intensity regions as early as 1 hour after intravenous injection of the MMP-2 probe, while contralateral MMP-2-negative tumors showed little to no signal intensity. A nonspecific control probe showed little to no activation in MMP-2-positive tumors.


CONCLUSIONS
It is feasible to image MMP-2 enzyme activity in vivo by using near-infrared optical imaging technology and "smart" matrix metalloproteinase-sensitive probes.
Bremer
C
C
Center for Molecular Imaging Research, Massachusetts General Hospital, Bldg 149, 13th St, Rm 5406, Charlestown, MA 02129, USA.
Bredow
S
S
Mahmood
U
U
Weissleder
R
R
Tung
C H
CH
D000818:Animals; D002623:Chemistry Techniques, Analytical / Q000379:methods; D005240:Feasibility Studies; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000201:enzymology*; D013057:Spectrum Analysis / Q000379:methods
D020778:Matrix Metalloproteinase 2