Preclinical evaluation of 99mTc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis

Abstract

PurposeIn previous in-vitro and ex-vivo studies we proved the specific uptake of 99mTc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of 99mTcCS in dogs. ProceduresThe radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20–40MBq/kg body weight of 99mTc by means of the tin method. In-vivo uptake of 99mTcCS was evaluated in dogs (n=12, castrated males, 4–9years, with 15–51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only. ResultsIn healthy control dogs we did not detect any specific uptake of 99mTcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented.Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls.In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I–III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of 99mTcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects. ConclusionThese results suggest that 99mTcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans.