Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate

In rheumatoid arthritis, articular infammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defned. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fuoro-PEG-folate, targeting folate receptor β (FRβ), to monitor systemic infammatory disease in liver and spleen of arthritic rats before and afer 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 signifcant (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 signifcantly (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 signifcantly 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 infammation in these organs. Macrophage PET imaging with [18F]fuoro-PEG-folate holds promise for detection of systemic infammation in RA as well as therapy (MTX) response monitoring.