Experiment design indicating analytic time points and methods for each experimental group. Forty 16-week-old male Wistar rats received three intraarticular papain injections (P.I.) and divided over two different groups: a sedentary group (n = 20) and a running group (n = 20). All running rats were subjected to a 6-week moderate running protocol, earlier reported to protect against OA . During the experiment, three μCT scans were made to measure longitudinal subchondral bone changes. At 6 and 12 weeks, a full analysis sequence was done in 10 animals per group (n†), consisting of: determination of activated macrophages by using SPECT/CT in vivo; and cartilage analysis with equilibrium partitioning of an ionic contrast agent by using (EPIC-)μCT and histology ex vivo.