Diagnosis of Arthritis Using Near-Infrared Fluorochrome Cy5.5

Purpose:Near-infrared range fluorescence (NIRF) imaging is a potential tool to diagnose biologic processes in vivo. This applicability study sought to define whether imaging with fluorochrome Cy5.5 can identify arthritis in murine antigen-induced arthritis (AIA). Materials and Methods:On day 7 of AIA (n = 9 mice), fluorescence intensities in inflamed and contralateral knee joints (the latter as internal control) were measured before and after intravenous injection of Cy5.5 (until 72 hours). Cy5.5 joint deposition was verified by confocal laser-scanning microscopy. Dye phagocytosis was evaluated in cultured macrophages (cell line PMJ2-R) by FACS analysis. Cy5.5 binding to serum protein was tested by NIRF scanning and gel electrophoresis. Results:Between 2 and 72 hours, the arthritic knee joints showed significantly higher fluorescence intensities compared with contralateral joints. Microscopy confirmed Cy5.5 deposition in the synovial membrane. Cultured macrophages actively phagocytosed Cy5.5. Cy5.5 bound mainly to albumin as the main serum protein. Conclusion:NIRF imaging with Cy5.5 can identify arthritic joints in vivo, likely due to nonspecific deposition.

[1]  W. Kaiser,et al.  In vivo imaging of experimental arthritis with near-infrared fluorescence. , 2004, Arthritis and rheumatism.

[2]  W. Kaiser,et al.  Noninvasive Diagnosis of Arthritis by Autofluorescence , 2003, Investigative radiology.

[3]  R. Landewé,et al.  Is radiographic progression a realistic outcome measure in clinical trials with early inflammatory arthritis? , 2003, Clinical and experimental rheumatology.

[4]  Carlo Bertucci,et al.  Reversible and covalent binding of drugs to human serum albumin: methodological approaches and physiological relevance. , 2002, Current medicinal chemistry.

[5]  Koen Vos,et al.  How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. , 2002, Arthritis and rheumatism.

[6]  R. Kinne,et al.  Systemic macrophage activation in locally-induced experimental arthritis. , 2001, Journal of autoimmunity.

[7]  Y. Toyama,et al.  Macrophage- and neutrophil- dominant arthritis in human IL-1α transgenic mice , 2001 .

[8]  W. Semmler,et al.  Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands , 2001, Nature Biotechnology.

[9]  P. Villiger,et al.  Rheumatoide Arthritis: Diagnose, Assessment und Qualitätskontrolle , 2001 .

[10]  W Semmler,et al.  Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes. , 2001, Bioconjugate chemistry.

[11]  Y. Toyama,et al.  Macrophage- and neutrophil-dominant arthritis in human IL-1 alpha transgenic mice. , 2001, The Journal of clinical investigation.

[12]  J. Schneider-Mergener,et al.  Cyanine Dye Labeled Vasoactive Intestinal Peptide and Somatostatin Analog for Optical Detection of Gastroenteropancreatic Tumors , 2000, Annals of the New York Academy of Sciences.

[13]  K. König,et al.  Multiphoton microscopy in life sciences , 2000, Journal of microscopy.

[14]  H. Mantsch,et al.  Noninvasive localization of tumors by immunofluorescence imaging using a single chain Fv fragment of a human monoclonal antibody with broad cancer specificity , 2000, Cancer.

[15]  J. Hamilton,et al.  Exacerbation of acute inflammatory arthritis by the colony‐stimulating factors CSF‐1 and granulocyte macrophage (GM)‐CSF: evidence of macrophage infiltration and local proliferation , 2000, Clinical and experimental immunology.

[16]  F. Breedveld,et al.  Immunohistological analysis of synovial tissue for differential diagnosis in early arthritis. , 1999, Rheumatology.

[17]  O. Wolfbeis,et al.  Synthesis, spectral properties, and detection limits of reactive squaraine dyes, a new class of diode laser compatible fluorescent protein labels. , 1999, Bioconjugate chemistry.

[18]  B. Bresnihan.  Pathogenesis of joint damage in rheumatoid arthritis. , 1999, The Journal of rheumatology.

[19]  P. Emery,et al.  The current status of ultrasonography in rheumatology. , 1999, Rheumatology.

[20]  G. Ekström,et al.  Physiological characterization of mBSA antigen induced arthritis in the rat. II. Joint blood flow, glucose metabolism, and cell proliferation. , 1998, The Journal of rheumatology.

[21]  R. Bräuer,et al.  Limiting dilution analysis of the frequency of autoreactive lymph node cells isolated from mice with antigen-induced arthritis. , 1996, Journal of autoimmunity.

[22]  B. Bresnihan,et al.  Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. , 1996, Arthritis and rheumatism.

[23]  J. Levick.  Microvascular Architecture and Exchange in Synovial Joints , 1995, Microcirculation.

[24]  H. Fassbender,et al.  Histomorphological basis of articular cartilage destruction in rheumatoid arthritis. , 1983, Collagen and related research.

[25]  J. Levick.  Permeability of rheumatoid and normal human synovium to specific plasma proteins. , 1981, Arthritis and rheumatism.

[26]  M. Vadas,et al.  [Antigen-induced arthritis in mice: genetic and immunologic studies]. , 1978, Verhandlungen der Deutschen Gesellschaft fur Rheumatologie.