123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis.

OBJECTIVE To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10), 123I-labeled, serine proteinase inhibitor antileukoproteinase (123I-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). METHODS Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 microg of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). 123I-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6). The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography. Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. RESULTS ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with AIA. In both knee joints, 123I-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. CONCLUSION Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA. These findings underscore the high sensitivity of 123I-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA.

[1]  J. V. van Meurs,et al.  Kinetics of aggrecanase- and metalloproteinase-induced neoepitopes in various stages of cartilage destruction in murine arthritis. , 1999, Arthritis and rheumatism.

[2]  G. Ekström,et al.  Physiological characterization of mBSA antigen induced arthritis in the rat. I. Vascular leakiness and pannus growth. , 1998, The Journal of rheumatology.

[3]  R. Kinne,et al.  Rat antigen-induced arthritis: cartilage alterations assessed with iodine-123-antileukoproteinase. , 1998, Journal of Nuclear Medicine.

[4]  Y W Bahk,et al.  Dual-head pinhole bone scintigraphy. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  Y. Saeki,et al.  Interleukin 6 plays a key role in the development of antigen-induced arthritis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Jamar,et al.  The importance of endothelium and interstitial fluid in nuclear medicine , 1998, European Journal of Nuclear Medicine.

[7]  I. Petersson,et al.  Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the patellofemoral joint , 1998, Annals of the rheumatic diseases.

[8]  D Mainard,et al.  Review: Magnetic resonance imaging of normal and osteoarthritic cartilage. , 1998, Arthritis and rheumatism.

[9]  R. Bräuer,et al.  Matrix metalloproteinases, IL-6, and nitric oxide in rat antigen-induced arthritis. , 1998, Clinical and experimental rheumatology.

[10]  R. Kinne,et al.  The serine proteinase inhibitor antileukoproteinase specifically accumulates in normal but not in arthritic cartilage. , 1997, The Journal of rheumatology.

[11]  E. Larsson,et al.  Detection of joint pathology by magnetic resonance imaging in patients with early rheumatoid arthritis. , 1997, British journal of rheumatology.

[12]  D. Felson,et al.  Defining the role of molecular markers to monitor disease, intervention, and cartilage breakdown in osteoarthritis. , 1997, The Journal of rheumatology.

[13]  Charles R. Meyer,et al.  Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations , 1997, Medical Image Anal..

[14]  W. Arend,et al.  The pathophysiology and treatment of rheumatoid arthritis. , 1997, Arthritis and rheumatism.

[15]  S. Wahl,et al.  Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinases. , 1997, The Journal of clinical investigation.

[16]  D. Radzioch,et al.  Secretory Leukocyte Protease Inhibitor: A Macrophage Product Induced by and Antagonistic to Bacterial Lipopolysaccharide , 1997, Cell.

[17]  P. Dieppe,et al.  Osteoarthritis in ankle and knee joints. , 1997, Seminars in arthritis and rheumatism.

[18]  T. A. Carpenter,et al.  Cartilage swelling and loss in a spontaneous model of osteoarthritis visualized by magnetic resonance imaging. , 1996, Osteoarthritis and cartilage.

[19]  F. Emmrich,et al.  Rat adjuvant arthritis: imaging with technetium-99m-anti-CD4 Fab' fragments. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  P. Mapp,et al.  Neurogenic influences on contralateral responses during experimental rat monoarthritis , 1995, Brain Research.

[21]  J. Hermans,et al.  Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor. , 1995, Thorax.

[22]  W. Murphy,et al.  Updated osteoarthritis reference standard. , 1995, The Journal of rheumatology. Supplement.

[23]  F. Emmrich,et al.  Induction of flare-up reactions in rat antigen-induced arthritis. , 1995, Journal of autoimmunity.

[24]  S. Henzgen,et al.  Different immunological mechanisms contribute to cartilage destruction in antigen-induced arthritis. , 1994, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[25]  E. Brodin,et al.  Weight bearing as an objective measure of arthritic pain in the rat. , 1994, Journal of pharmacological and toxicological methods.

[26]  K. Erlandsson,et al.  Small animal imaging with pinhole single‐photon emission computed tomography , 1994, Cancer.

[27]  D. A. Walsh,et al.  Monoarthritis in the rat knee induces bilateral and time-dependent changes in substance P and calcitonin gene-related peptide immunoreactivity in the spinal cord , 1993, Neuroscience.

[28]  T. Aigner,et al.  The serine-protease inhibitor of cartilage matrix is not a chondrocytic gene product. , 1992, European journal of biochemistry.

[29]  S. Lohmander,et al.  Markers of cartilage metabolism in arthrosis. A review. , 1991, Acta orthopaedica Scandinavica.

[30]  H. Burkhardt,et al.  Purification of a serine-proteinase inhibitor from human articular cartilage. Identity with the acid-stable proteinase inhibitor of mucous secretions. , 1991, The Biochemical journal.

[31]  K. Ohlsson,et al.  Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[32]  F. Lottspeich,et al.  The acid‐stable proteinase inhibitor of human mucous secretions (HUSI‐I, antileukoprotease) , 1986, FEBS letters.

[33]  P. Fraker,et al.  Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. , 1978, Biochemical and biophysical research communications.

[34]  T. Cooke,et al.  The pathogenesis of chronic inflammation in experimental antigen-induced arthritis. I. The role of antigen on the local immune response. , 1972, Arthritis and rheumatism.

[35]  L. Glynn,et al.  The production of arthritis in rabbits by an immunological reaction to fibrin. , 1962, British journal of experimental pathology.

[36]  N. Beckmann,et al.  High-resolution three-dimensional magnetic resonance imaging for the investigation of knee joint damage during the time course of antigen-induced arthritis in rabbits. , 1999, Arthritis and rheumatism.

[37]  D Loeuille,et al.  In vitro magnetic resonance microimaging of experimental osteoarthritis in the rat knee joint. , 1997, The Journal of rheumatology.

[38]  F. Emmrich,et al.  Joint uptake and body distribution of a technetium-99m-labeled anti-rat-CD4 monoclonal antibody in rat adjuvant arthritis. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.