title: In vivo quantitative measurement of arthritis activity based on  hydrophobically modified glycol chitosan in inflammatory arthritis: more active than passive  accumulation.
abstract: We demonstrated that arthritis could be visualized noninvasively using hydrophobically modified glycol chitosan nanoparticles labeled with Cy5.5 (HGC-Cy5.5) and an optical imaging system. Activated macrophages expressing Mac-1 molecules effectively phagocytosed HGC-Cy5.5, which formed spherical nanoparticles under physiologic conditions. We estimated the applicability of HGC-Cy5.5 to quantitative analysis of arthritis development and progression. Near-infrared fluorescence images, captured after HGC-Cy5.5 injection in mice with collagen-induced arthritis, showed stronger fluorescence intensity in the active arthritis group than in the nonarthritis group. According to the progression of arthritis in both collagen-induced arthritis and collagen antibody-induced arthritis models, total photon counts (TPCs) increased in parallel with the clinical arthritis index. Quantitative analysis of fluorescence after treatment with methotrexate showed a significant decrease in TPC in a dose-dependent manner. Histologic evaluation confirmed that the mechanism underlying selective accumulation of HGC-Cy5.5 within synovitis tissues included enhanced phagocytosis of the probe by Mac-1-expressing macrophages as well as enhanced permeability through leaky vessels. These results suggest that optical imaging of arthritis using HGC-Cy5.5 can provide an objective measurement of disease activity and, at the same time, therapeutic responses in rheumatoid arthritis.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, Hawolgok-dong, Seongbuk-gu, Seoul.
authors.forename: Kyeong Soon
authors.initials: KS
authors.lastname: Park
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: Keum Hee
authors.initials: KH
authors.lastname: Sa
authors.forename: Hee Beom
authors.initials: HB
authors.lastname: Koo
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Eon Jeong
authors.initials: EJ
authors.lastname: Nam
authors.forename: In Chan
authors.initials: IC
authors.lastname: Youn
authors.forename: Kwang Meyung
authors.initials: KM
authors.lastname: Kim
authors.forename: In San
authors.initials: IS
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kui Won
authors.initials: KW
authors.lastname: Choi
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D016022:Case-Control Studies; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D053758:Nanoparticles / Q000737:chemistry; D061848:Optical Imaging / Q000379:methods*; D010587:Phagocytosis; D011897:Random Allocation; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013582:Synovial Fluid / Q000166:cytology
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; C118638:glycol-chitosan; D048271:Chitosan; D008727:Methotrexate