99mTc-NTP 15-5 imaging for cartilage involvement in experimental rheumatoid arthritis: Comparison with routinely used molecular imaging methods and sensitivity to chronic nonsteroidal antiinflammatory drug treatment

Abstract

This study determined, using the intraarticular complete Freund adjuvant arthritis mice model, whether the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) targeting proteoglycans has a pathophysiologic validity for in vivo imaging of rheumatoid arthritis (RA) and its response to chronic nonsteroidal antiinflammatory drugs. Methods: We investigated the time course of cartilage remodeling by99m Tc-NTP 15-5 scintigraphy, bone damages by 99mTc-hydroxymethylene diphosphonate imaging, inflammation by 18F-FDG PET, and joint proteoglycan content and pain behavior in animals, without and with meloxicam treatment. Paw circumference, thermal pain behavior, and histology as well as proteoglycan content of the whole joint were determined. Results: 99mTc-NTP 15-5 showed specific tracer accumulation within RA joints, with a significant increase in scintigraphic ratio observed in RA versus shams from day 3 to day 28. 18F-FDG evidenced uptake in RA joints from day 15 to day 29. Animals treated with meloxicam (5 mg/kg) exhibited a dose-dependent decrease in both 99mTc-NTP 15-5 and 18F-FDG uptake ratios versus saline-treated animals. 99mTc-hydroxymethylene diphosphonate bone scans were only positive at day 14 in RA versus shams, with a significant effect of meloxicam. An increase in proteoglycans of RA joint and thermal pain behavior were observed and were dose-dependently reduced by meloxicam. Conclusion: These experimental results bring data in favor of the 99mTc-NTP 15-5 radiotracer for assessing, in vivo, cartilage remodeling in RA that could be used to monitor therapy.