title: Arthritis imaging using a near-infrared fluorescence folate-targeted probe.
abstract: A recently developed near-infrared fluorescence-labeled folate probe (NIR2-folate) was tested for in vivo imaging of arthritis using a lipopolysaccharide intra-articular injection model and a KRN transgenic mice serum induction mouse model. In the lipopolysaccharide injection model, the fluorescence signal intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between lipopolysaccharide-treated and control joints. The fluorescence signal intensity of the NIR2-folate probe at the inflammatory joints was found to be significantly higher than the control normal joints (up to 2.3-fold, P < 0.001). The NIR2-free dye injection group showed a persistent lower enhancement ratio than the NIR2-folate probe injection group. Excessive folic acid was also given to demonstrate a competitive effect with the NIR2-folate. In the KRN serum transfer model (n = 4), NIR2-folate was applied at different time points after serum transfer, and the inflamed joints could be detected as early as 30 hours after arthritogenic antibody transfer (1.8-fold increase in signal intensity). Fluorescence microscopy, histology, and immunohistochemistry validated the optical imaging results. We conclude that in vivo arthritis detection was feasible using a folate-targeted near-infrared fluorescence probe. This receptor-targeted imaging method may facilitate improved arthritis diagnosis and early assessment of the disease progress by providing an in vivo characterization of active macrophage status in inflammatory joint diseases.
authors.affiliation: Center of Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Wei-Tsung
authors.initials: WT
authors.lastname: Chen
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005240:Feasibility Studies; D005456:Fluorescent Dyes / Q000032:analysis*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D013582:Synovial Fluid / Q000166:cytology
chemical_list: D002352:Carrier Proteins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D008070:Lipopolysaccharides; C506173:NIR2-folate; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D005492:Folic Acid
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