TY - JOUR T1 - Inflammatory Cytokines and Hypoxia Contribute to <sup>18</sup>F-FDG Uptake by Cells Involved in Pannus Formation in Rheumatoid Arthritis JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 920 LP - 926 DO - 10.2967/jnumed.108.060103 VL - 50 IS - 6 AU - Tamiko Matsui AU - Norihito Nakata AU - Shigenori Nagai AU - Akira Nakatani AU - Miwako Takahashi AU - Toshimitsu Momose AU - Kuni Ohtomo AU - Shigeo Koyasu Y1 - 2009/06/01 UR - http://jnm.snmjournals.org/content/50/6/920.abstract N2 - Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. 18F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between 18F-FDG accumulation and RA pathology, we assessed 18F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and 3H-FDG uptake in vitro using various cells involved in arthritis. Methods: 18F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the 18F-FDG accumulation was compared with the histologic findings. 3H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to 18F-FDG accumulation. In addition, the influence on 3H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor α [TNFα], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. Results: 18F-FDG PET depicted swollen joints, and 18F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of 18F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro 3H-FDG uptake assay, fibroblasts showed the highest 3H-FDG uptake, followed by neutrophils. Although only a small amount of 3H-FDG was incorporated by resting macrophages, a dramatic increase in 3H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFα and IL-1, and hypoxia. Although neutrophils showed relatively high 3H-FDG uptake without activation, no increase in 3H-FDG uptake was observed in response to inflammatory cytokines. 3H-FDG uptake by T cells was much lower than that by other cells. Thus, fibroblasts and activated macrophages contribute to a high level of 18F-FDG accumulation in the pannus, and hypoxia as well as cytokine stimulation significantly increases 18F-FDG uptake by these cells. Conclusion: 18F-FDG accumulation in RA reflects proliferating pannus and inflammatory activity enhanced by inflammatory cytokines and hypoxia. 18F-FDG PET should be effective for quantifying the inflammatory activity of RA. ER -