Macrophage activation determined in sedentary (round boxes) and running (square boxes) rats by injection of [111In]-DOTA-Bz-folate by using SPECT/CT. (A) Quantitative outcome of measured radioactivity in the control (blank boxes) and papain-injected (gray boxes) knee joints normalized to the size of the cylindrical region of interest (kBq/mm3). Absolute differences per animal were calculated (kBq/mm3) to reduce interindividual variation (black boxes). A high radioactivity is related to more macrophage activation. (B) Ectopic bone formation (mm3) as a measure for osteophyte development was quantified on longitudinal bone μCT scans. (C) Sagittal SPECT/CT images of knee joints from representative animals. CT images shown in black and white were used for anatomic reference; the SPECT images are shown in color. Transaxial images from patellar bone extracted from binary μCT images show ectopic bone formation (red color). *P < 0.05; **P < 0.01; ***P < 0.001; error bars indicate 95% confidence intervals.