Background and objectives Monitoring response to therapy in arthritis is usually carried out by clinical assessment, ultrasonography, conventional radiography or MRI. Molecular imaging could be used to more specifically monitor therapy response, thus enabling tailored therapy regimens and enhancing therapeutic outcome. Here, we hypothesised that response to etanercept could be monitored by radionuclide imaging in arthritic mice. We tested three different targets namely fibroblast activation protein (FAP), F4/80-expressing macrophages, and integrin αvβ3.
Materials and methods Male DBA/1J mice with collagen-induced arthritis were treated with etanercept. SPECT/CT (Single photon emission computed tomography/ X-ray computed tomography) scans were acquired at 1, 24 and 48 h after injecting 111In-RGD2 (integrin αvβ3), 111In-anti-F4/80-A3–1 (anti-murine macrophage antibody), or 111In-28H1 (anti-FAP antibody), respectively, with nonspecific controls included. Mice were dissected after the last scan and scans were analysed quantitatively and were correlated with macroscopic scoring.
Results Experimental arthritis in DBA-1J mice was imaged with 111In-28H1 (anti-FAP), 111In-anti-F4/80-A3–1, and 111In-RGD2. Tracer uptake in joints correlated signifianty with arthritis score. Treatment decreased joint uptake of tracers; it decreased from 23 ± 15%ID/g, 8 ± 4%ID/g, 2 ± 1%ID/g to 11 ± 11%ID/g (p < 0.001), 4 ± 4%ID/g (p < 0.001), 1 ± 0.2%ID/g (p < 0.01) for 111In-28H1, 111In-anti-F4/80-A3–1, and 111In-RGD2, respectively. Arthritis-to-blood ratios (in mice with established arthritis) were higher for 111In-28H1 (5.5 ± 1), 111In-anti-F4/80-A3–1 (10.4 ± 4), and 111In-RGD2 (7.2 ± 1)than for control 111In-DP47GS (0.7 ± 0.5; p = 0.002), 111In-rat IgG2b (0.5 ± 0.2; p = 0.002), or co-injection of excess RGD2, (3.5), indicating specific uptake of all tracers in arthritic joints.
Conclusions In conclusion, 111In-28H1, 111In-anti-F4/80-A3–1, and 111In-RGD2 can be used to specifically monitor therapy response in experimental arthritis at the molecular level. Not only does this highlight the originality of the studies carried out here, by targeting integrins, macrophages or FAP in preclinical models of arthritis, but also the novelty of assessing these tracers as tools to monitor therapy response. Further studies need to be carried out to determine whether these tracers could be used for early diagnosis of arthritis as well as whether they can be used to monitor response to other types of therapies.
- experimental arthritis
- fibroblast activation protein
- RGD peptide
- therapy response