Ex-vivo Evaluation of 99mTc Labeled Glucosamine Sulfate(99mTcGS) in Articular Cartilage. Relevance for Osteoarthritis Imaging
Journal Title: Journal of Orthopedics & Rheumatology - Year 2014, Vol 1, Issue 3
Abstract
Background: Glucosamine sulfate (GS) is widely used in the treatment of osteoarthritis, but no data concerning the local uptake of GS in articular cartilage exist. For this reason we performed radiolabeling of GS (Rottapharm, Monza, Italy) using the 99mTcO4-/t in method and investigated its uptake in articular cartilage. Methods: Radiolabeling of GS is difficult, because of the small MW of GS (450 Da) and of 99mTcO4 - for separation after radiolabeling. For uptake studies, articular surgery tissue from patients (n=6, 68-79a) undergoing knee arthroplasty (pieces of ~3 mg wet weight), or frozen tissue sections (10 μ) for autoradiography (10 μCi) were used. The uptake of 99mTcGS was monitored from 0.5 to 72 h of incubation to achieve saturation, by quantitation of radioactivity with a Gammacounter or autoradiography. To mimic in-vivo treatment, tissue pieces were preincubated with cold GS (80 μg/ml) for 16 weeks prior to incubation with 99mTcGS. The incubation was performed with tissues with different degree of degeneration. Results: The best radiolabeling results were obtained using 25 mg of GS, 120-150 MBq of 99mTc, separation on G10 column, specific activity of 162.2-202.8 mCi/mM, n=6. The uptake was time-dependent and amounted to a maximum of 77.4. -71.7% at 48 h versus 72 h, at saturation. Saturation was achieved already after 24 h of incubation. When the tissue was preincubated with cold GS the subsequent uptake of 99mTcGS was strongly reduced by 52.3-71.8%, proving the chondrotropic effects of GS during preincubation. The reduction of 99mTcGS uptake was observed also in areas of different grades of degeneration from the same patient by 27.8-35.8%, proving the specificity of uptake. Autoradiographic studies paralleled the uptake in tissue pieces. We performed a statistical evaluation of differences between all investigated OA patients with different degree of cartilage degeneration. For these patients we evaluated the autoradiographic uptake at all experimental points of incubation times (1 h, 3 h, 6 h, 24 h, 48 h). 99mTcGS uptake in tissues of different extent of degeneration varied significantly during the whole time of incubation, the more degenerated regions showing a significantly higher 99mTcGS uptake. The non-specific uptake in the presence of 50-fold excess of cold GS was increasing with time up to a maximum of about 10%, at saturation. Conclusions: 99mTcGS could be a suitable tracer to quantify degeneration in articular cartilage, because of its high uptake and specificity. It could be a potential candidate for imaging osteoarthritis in cartilage and possibly for monitoring therapeutic effects.
Authors and Affiliations
Grazyna Sobal
Keywords
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