Uptake studies with chondrotropic 99mTc-chondroitin sulfate in articular cartilage. Implications for imaging osteoarthritis in the knee

Chondroitin sulfate (CS) is an endogenous component of extracellular matrix in the cartilage and can be valuable for imaging of cartilage degeneration after radiolabeling. Data monitoring the uptake of 99mTcCS by human cartilage are rare. Radiolabeling was performed by 99mTcO4−/tin method at pH 5.0 in 0.5 M sodium acetate. For uptake studies human articular cartilage (n = 4, 65-79a) derived from individuals undergoing knee replacement (pieces of 3-5 mg wet weight), or frozen tissue sections (5 μ) for autoradiography (10 μCi) were used. The uptake was monitored from 10 min up to 96 h to achieve saturation. As the commercially available drug Condrosulf (IBSA, Lugano) contains Mg-stearate (0.25%) as additive (to improve its gastrointestinal resorption), we investigated the uptake ± additive. The washout of the tracer was examined by tissue incubation after uptake experiments (3 h and 24 h) with PBS-buffer for 10 min to 3 h. Using human articular cartilage the maximal uptake of 99mTcCS (specific activity of 4.1-6.1 Ci/mmol) was continuously increasing with time amounting to a maximum of 53.2% ± 3.2% with additive, versus 39.4% ± 2.3%, without additive, at saturation. Additive increased the resorption of the drug and consecutively its uptake. The washout of the tracer from cartilage after 3 h uptake amounted to 1.5% ± 0.2% with additive, versus 2.6% ± 0.5%, without. After 24 h washout was lower amounting to 1.1% ± 0.1% versus 1.75% ± 0.15%, respectively. Autoradiography revealed also a continuous increase in uptake of 99mTcCS with time. After 10 min of incubation the uptake increase was proportional to the incubation time, reaching the maximum at 48-72 h. Enhanced uptake at the surface (superficial zone) as compared to the subchondral part (deep zone) of slices, was observed. The non-specific uptake in the presence of 50-fold excess of cold CS was time-dependent up to a maximum of 15% (tissue) and 10% (autoradiography), at saturation. The uptake studies indicate, that 99mTcCS accumulates in articular cartilage and prove its chondrotropic effects.