Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3.

Autor:	Terry SY; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Department of Imaging Chemistry and Biology, King's College London, London, United Kingdom samantha.terry@kcl.ac.uk., Koenders MI; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Franssen GM; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Nayak TK; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland; and., Freimoser-Grundschober A; Roche Innovation Center Zurich, Zurich, Switzerland., Klein C; Roche Innovation Center Zurich, Zurich, Switzerland., Oyen WJ; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Boerman OC; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Laverman P; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2016 Mar; Vol. 57 (3), pp. 467-72. Date of Electronic Publication: 2015 Dec 03.
DOI:	10.2967/jnumed.115.162628
Abstrakt:	Unlabelled: 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 (111)In-RGD2 (integrin αvβ3), (111)In-anti-F4/80-A3-1 (antimurine macrophage antibody), or (111)In-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 (111)In-28H1 (anti-FAP), (111)In-anti-F4/80-A3-1, and (111)In-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 < 0.001), 4 ± 4 (P < 0.001), and 1 ± 0.2 %ID/g (P < 0.01) for (111)In-28H1, (111)In-anti-F4/80-A3-1, and (111)In-RGD2, respectively. Arthritis-to-blood ratios (in mice with arthritis score 2 per joint) were higher for (111)In-28H1 (5.5 ± 1; excluding values > 25), (111)In-anti-F4/80-A3-1 (10.4 ± 4), and (111)In-RGD2 (7.2 ± 1) than for control (111)In-DP47GS (0.7 ± 0.5; P = 0.002), (111)In-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: (111)In-28H1, (111)In-anti-F4/80-A3-1, and (111)In-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. (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu