Abstract
Background In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptor β (FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. Methods [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβ expression. Results [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p < 0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p < 0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold, p < 0.005) and spleen (3-fold, p < 0.01) of MTX- versus saline-treated rats. Conclusions MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease involving mainly the synovium of the joints, other tissue/organ involvement has been recognized [1, 2]
In the present study we extend on these observations by exploiting [18F]fluoro-Polyethylene glycol standard deviation (SD) (PEG)-folate Positron Emission Tomography (PET) to monitor potential systemic inflammation in liver and spleen of arthritic rats before and after MTX therapy, hypothesizing that MTX therapy impacts systemic inflammatory effects in the organs
In a recent study we showed that imaging with the macrophage tracer [18F]fluoroPEG-folate could visualize decreased accumulation of the tracer in the knee joints of arthritic rats treated with MTX
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease involving mainly the synovium of the joints, other tissue/organ involvement has been recognized [1, 2]. Early detection and treatment of systemically affected organs in RA could benefit in achieving predefined low disease activity and remission [5, 6] To this end, in a preclinical setting, animal models of arthritis may serve a valuable tool for imaging (extra) articular and nonarticular inflammation and for monitoring the response to therapeutic interventions. We examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptor β (FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p < 0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
