Imaging of a rat osteoarthritis model using 18F-fluoride positron emission tomography

Currently, conventional radiography is the standard method for the diagnosis and evaluation of the severity of osteoarthritis (OA), but it takes a couple of years to detect cartilage loss. Magnetic resonance imaging can delineate articular cartilage and accurately assess cartilage volume and thickness, but its reliability for very early diagnosis of OA is still controversial. The purpose of this study was to confirm the potential of F-18-fluoride PET for the early diagnosis of OA by using a surgically induced rat OA model. Seventeen 16-week-old male Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT) in the right knee to induce OA. The left knee underwent sham operation. At 2, 4, and 8 weeks after operation, the rats were injected with 2.5 MBq/kg of F-18-fluoride, and 30 min after injection, each rat was killed and the bilateral knees were resected. The femur and tibia were cut horizontally, approximately 2 mm from the joint surface excluding the growth plate, and were cut into the medial and lateral condyles. The patella was also resected and blood samples were collected. The radioactivity of each sample was measured by gamma counting. Assays for serum cartilage oligomeric matrix protein and serum C-telopeptide of type II collagen were performed. Histopathological grading was performed according to a modified Mankin's scoring system. Two rats underwent PET scans at 2, 4, and 8 weeks after operation. The rats were injected with 30 MBq of F-18-fluoride, and 30 min after injection, bilateral knee images with a 30-min acquisition time were obtained with an animal PET system. The uptake of F-18-fluoride was significantly higher in ACLT knees than sham-operated knees in the medial femur and medial tibia at 2 weeks after operation. At 4 weeks after operation, the medial femur, medial tibia, and lateral tibia of OA knees showed significantly higher uptake of F-18-fluoride compared with sham-operated knees. At 8 weeks, all sections showed significant differences. The uptake of F-18-fluoride significantly increased as time elapsed in all sections. Uptake showed a significant correlation with histological scores. Our results suggest that F-18-fluoride is potentially useful for the early detection of osteoarthritic changes.