Optimization of matrix metalloproteinase fluorogenic probes for osteoarthritis imaging.
Among the classical collagenases, matrix metalloproteinase-13 (called MMP-13, collagenase-3) is one of the most important components for cartilage destruction of osteoarthritis (OA) developments. Despite many efforts, the detection methods of MMP-13 activity have been met with limited success in vivo, in part, due to the low sensitivity and low selectivity by homology of MMP family. Previously, we demonstrated the use of strongly dark-quenched fluorogenic probe allowed for the visual detection of MMP-13 in vitro and in OA-induced rat models. In this study, we described the optimization of MMP-13 fluorogenic probe for OA detection in vivo. Three candidate probes demonstrated recovered fluorescent intensity proportional with MMP-13 concentrations, respectively; however, Probe 2 exhibited both high signal amplification and selective recognition for MMP-13, not MMP-2 and MMP-9 in vitro. When Probe 2 was applied to OA-induced rat models, clear visualization of MMP-13 activity in OA-induced cartilage was obtained. Optimized MMP-13 fluorogenic probe can be applied to detect and image OA and have potential for evaluating the in vivo efficacy of MMP-13 inhibitors which are being tested for therapeutic treatment of OA.
Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
Ju Hee
JH
Ryu
Aeju
A
Lee
Jin Hee
JH
Na
Seulki
S
Lee
Hyung Jun
HJ
Ahn
Jong Woong
JW
Park
Cheol-Hee
CH
Ahn
Byung-Soo
BS
Kim
Ick Chan
IC
Kwon
Kuiwon
K
Choi
Inchan
I
Youn
Kwangmeyung
K
Kim
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D053509:Matrix Metalloproteinase 13 / Q000032:analysis* / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism*; D010003:Osteoarthritis / Q000175:diagnosis / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D015335:Molecular Probes; D010455:Peptides; D053509:Matrix Metalloproteinase 13