RT Journal Article
SR Electronic
T1 Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α<sub>v</sub>β<sub>3</sub>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 467
OP 472
DO 10.2967/jnumed.115.162628
VO 57
IS 3
A1 Terry, Samantha Y.A.
A1 Koenders, Marije I.
A1 Franssen, Gerben M.
A1 Nayak, Tapan K.
A1 Freimoser-Grundschober, Anne
A1 Klein, Christian
A1 Oyen, Wim J.
A1 Boerman, Otto C.
A1 Laverman, Peter
YR 2016
UL http://jnm.snmjournals.org/content/57/3/467.abstract
AB Rheumatoid arthritis is an autoimmune disease resulting in chronic synovial inflammation. Molecular imaging could be used to monitor therapy response, thus enabling tailored therapy regimens and enhancing therapeutic outcome. Here, we hypothesized that response to etanercept could be monitored by radionuclide imaging in arthritic mice. We tested 3 different targets, namely fibroblast activation protein (FAP), macrophages, and integrin αvβ3. Methods: Male DBA/1J mice with collagen-induced arthritis were treated with etanercept. SPECT/CT scans were acquired at 1, 24, and 48 h after injection of 111In-RGD2 (integrin αvβ3), 111In-anti-F4/80-A3-1 (antimurine macrophage antibody), or 111In-28H1 (anti-FAP antibody), respectively, with nonspecific controls included. Mice were dissected after the last scan, and scans were analyzed quantitatively and were correlated with macroscopic scoring. Results: Experimental arthritis was imaged with 111In-28H1 (anti-FAP), 111In-anti-F4/80-A3-1, and 111In-RGD2. Tracer uptake in joints correlated with arthritis score. Treatment decreased joint uptake of tracers from 23 ± 15, 8 ± 4, and 2 ± 1 percentage injected dose per gram (%ID/g) to 11 ± 11 (P &lt; 0.001), 4 ± 4 (P &lt; 0.001), and 1 ± 0.2 %ID/g (P &lt; 0.01) for 111In-28H1, 111In-anti-F4/80-A3-1, and 111In-RGD2, respectively. Arthritis-to-blood ratios (in mice with arthritis score 2 per joint) were higher for 111In-28H1 (5.5 ± 1; excluding values &gt; 25), 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 coinjection of excess RGD2 (3.5), indicating specific uptake of all tracers in arthritic joints. Conclusion: 111In-28H1, 111In-anti-F4/80-A3-1, and 111In-RGD2 can be used to specifically monitor the response to therapy in experimental arthritis at the molecular level. Further studies, however, still need to be performed.