PMID- 22127700 OWN - NLM STAT- MEDLINE DCOM- 20120127 LR - 20191210 IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 63 IP - 12 DP - 2011 Dec TI - Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe. PG - 3824-32 LID - 10.1002/art.30628 [doi] AB - OBJECTIVE: Early treatment based on an early diagnosis of rheumatoid arthritis (RA) could halt progression of the disease, but early diagnosis is often difficult. Matrix metalloproteinase 3 (MMP-3) is thought to be particularly important in the pathogenesis of RA. The aim of this study was to investigate whether an MMP-3-specific polymeric probe could be used for early diagnosis and for visualizing the progression of arthritis, using a near-infrared fluorescence (NIRF) imaging system. METHODS: The MMP-3-specific polymeric probe was developed by conjugating NIRF dye, MMP substrate peptide, and dark quencher to self-assembled chitosan nanoparticles. One hour after intravenous administration of the probe, fluorescent images of mice with collagen-induced arthritis at different stages of disease development were obtained. The correlation between the fluorescence recovered in in vivo imaging when using an MMP-3-specific polymeric probe and up-regulated MMP-3 activity in the joint tissues was evaluated by Western blotting and immunohistochemical staining. Histologic analysis and micro-computed tomography (micro-CT) were also used to assess arthritis progression. RESULTS: A significantly higher NIRF signal was recovered from arthritic joints compared with normal joints at 14 days after the first immunization, before any erythema or swelling could be observed with the naked eye or any erosion was detected by histologic analysis or micro-CT. The results of immunohistochemical analysis and Western blotting confirmed that the fluorescence recovered in the in vivo imaging was related to up-regulated MMP-3 activity in the joint tissues. CONCLUSION: An MMP-3-specific polymeric probe provided clear early diagnosis of arthritis and visualization of arthritis progression using an NIRF imaging system. This approach could be used for early diagnosis and for monitoring drug and surgical therapies in individual cases. CI - Copyright (c) 2011 by the American College of Rheumatology. FAU - Ryu, Ju Hee AU - Ryu JH AD - Korea Institute of Science and Technology, Seoul, and Seoul National University, Seoul, Republic of Korea. FAU - Lee, Aeju AU - Lee A FAU - Chu, Jun-Uk AU - Chu JU FAU - Koo, Heebeom AU - Koo H FAU - Ko, Chang-Yong AU - Ko CY FAU - Kim, Han Sung AU - Kim HS FAU - Yoon, Soo-Young AU - Yoon SY FAU - Kim, Byung-Soo AU - Kim BS FAU - Choi, Kuiwon AU - Choi K FAU - Kwon, Ick Chan AU - Kwon IC FAU - Kim, Kwangmeyung AU - Kim K FAU - Youn, Inchan AU - Youn I LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Biomarkers) RN - 0 (Fluorescent Dyes) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Arthritis, Experimental/*diagnosis/*metabolism/pathology MH - Arthrography MH - Biomarkers/metabolism MH - Diagnostic Imaging/*methods MH - Disease Models, Animal MH - Disease Progression MH - *Early Diagnosis MH - Fluorescent Dyes/*metabolism MH - Knee Joint/metabolism/pathology MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Mice MH - Mice, Inbred DBA MH - Nanoparticles MH - Tomography, X-Ray Computed EDAT- 2011/12/01 06:00 MHDA- 2012/01/28 06:00 CRDT- 2011/12/01 06:00 PHST- 2011/12/01 06:00 [entrez] PHST- 2011/12/01 06:00 [pubmed] PHST- 2012/01/28 06:00 [medline] AID - 10.1002/art.30628 [doi] PST - ppublish SO - Arthritis Rheum. 2011 Dec;63(12):3824-32. doi: 10.1002/art.30628.