OBJECTIVE: To determine the utility of intercellular adhesion molecule (ICAM)-1 antibody-conjugated gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA-anti-ICAM-1) as a targeted contrast agent for the molecular magnetic resonance imaging (MRI) in collagen-induced arthritis (CIA). MATERIALS AND METHODS: Three groups of mice were used: non-arthritic normal, CIA mice in both the early inflammatory and chronic destructive phases. The MR images of knee joints were obtained before and after injection of Gd-DTPA-anti-ICAM-1, Gd-DTPA, and Gd-DTPA-Immunoglobulin G (Ig G) and were analyzed quantitatively. The patterns of enhancement on the MR images were compared with the histological and immunohistochemical ICAM-1 staining. RESULTS: The images obtained after injection of Gd-DTPA-anti-ICAM-1 displayed gradually increasing signal enhancement from the moment following injection (mean +/- standard deviation [SD]: 424.3 +/- 35.2, n = 3) to 24 hours (532 +/- 11.3), rather than on pre-enhanced images (293 +/- 37.6) in the early inflammatory phase of CIA mice. However, signal enhancement by Gd-DTPA and Gd-DTPA-IgG disappeared after 80 minutes and 24 hours, respectively. In addition, no significant enhancement was seen in the chronic destructive phase of CIA mice, even though they also showed inflammatory changes on T2-weighted MR images. ICAM-1 expression was demonstrated in the endothelium and proliferating synovium of the early inflammatory phase of CIA mice, but not in the chronic destructive phase. CONCLUSION: Molecular MRI with Gd-DTPA-anti-ICAM-1 displays specific images targeted to ICAM-1 that is expressed in the inflamed synovium of CIA. This novel tool may be useful for the early diagnosis and differentiation of the various stages of rheumatoid arthritis.
Animals ; Arthritis, Experimental/*metabolism ; Collagen ; Contrast Media ; Disease Models, Animal ; Gadolinium DTPA/diagnostic use ; Intercellular Adhesion Molecule-1/*metabolism ; Knee Joint/*metabolism/radiography ; Magnetic Resonance Imaging/*methods ; Male ; Mice ; Synovial Membrane/*metabolism/radiography

Calcium Pyrophosphate ; metabolism ; Cartilage, Articular ; metabolism ; pathology ; Chondrocalcinosis ; diagnostic imaging ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Gout ; pathology ; Humans ; Knee Joint ; diagnostic imaging ; metabolism ; pathology ; Male ; Menisci, Tibial ; metabolism ; pathology ; Middle Aged ; Osteoarthritis ; etiology ; pathology ; Radiography

No abstract available.
Arthritis, Gouty/drug therapy/*metabolism/*radiography ; Calcium Pyrophosphate/*analysis ; Crystallization ; Female ; Glucocorticoids/administration & dosage ; Humans ; Injections, Intra-Articular ; Knee Joint/*chemistry/drug effects/*radiography ; Middle Aged ; Predictive Value of Tests ; Tomography, X-Ray Computed/*methods ; Treatment Outcome ; Triamcinolone/administration & dosage

PURPOSE: The aim of this study was to determine the relationship of hypoxia-inducible factor-2 (HIF-2α) and vascular endothelial growth factor (VEGF) with radiographic severity in primary osteoarthritis (OA) of the knee. Expression of these two factors in cartilage samples from OA knee joints was examined at mRNA and protein levels. MATERIALS AND METHODS: Knee joints were examined using plain radiographs, and OA severity was assessed using the Kellgren and Lawrence (KL) grading system. Specimens were collected from 29 patients (31 knees) who underwent total knee replacement because of severe medial OA of the knee (KL grades 3 and 4), 16 patients who underwent knee arthroscopy (KL grade 2), and 5 patients with traumatic knees (KL grade 0). HIF-2α and VEGF expression was quantified by real-time polymerase chain reaction and western blotting. RESULTS: Cartilage degeneration correlated with the radiographic severity grade. OA severity, determined using the Mankin scale, correlated positively with the KL grade (r=0.8790, p<0.01), and HIF-2α and VEGF levels with the radiographic severity of knee OA (r=0.7001, p<0.05; r=0.6647, p<0.05). CONCLUSION: In OA cartilage, HIF-2α and VEGF mRNA and protein levels were significantly and positively correlated. The expression of both factors correlated positively with the KL grade. HIF-2α and VEGF, therefore, may serve as biochemical markers as well as potential therapeutic targets in knee OA.
Adult ; Aged ; Arthroplasty, Replacement, Knee ; Arthroscopy ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Biomarkers/*blood ; Cartilage/*metabolism ; Female ; Humans ; Knee Joint/*diagnostic imaging ; Male ; Middle Aged ; Osteoarthritis, Knee/*blood/diagnostic imaging/physiopathology ; RNA, Messenger ; Radiography ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Vascular Endothelial Growth Factor A/*metabolism