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NIRF-Molecular Imaging with Synovial Macrophages-Targeting Vsig4 Nanobody for Disease Monitoring in a Mouse Model of Arthritis

Tijdschriftbijdrage - Tijdschriftartikel

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.

Tijdschrift: International Journal of Molecular Sciences
ISSN: 1661-6596
Issue: 13
Volume: 20
Jaar van publicatie:2019
Trefwoorden:Animals, Arthritis, Experimental/diagnosis, Fluorescent Antibody Technique, Fluorescent Dyes/chemistry, Immunohistochemistry, Macrophages/immunology, Male, Mice, Microscopy, Fluorescence, Models, Molecular, Molecular Imaging/methods, Molecular Structure, Receptors, Complement/immunology, Single-Domain Antibodies/chemistry, Spectroscopy, Near-Infrared, Staining and Labeling, Synovial Membrane/immunology, Multidisciplinaire scheikunde , Biochemie & -fysica en Moleculaire biologie