TY - JOUR
T1 - Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [ 18 F]Fluoro-PEG-Folate
AU - Chandrupatla, Durga M.S.H.
AU - Jansen, Gerrit
AU - Mantel, Elise
AU - Low, Philip S.
AU - Matsuyama, Takami
AU - Musters, René P.
AU - Windhorst, Albert D.
AU - Lammertsma, Adriaan A.
AU - Molthoff, Carla F.M.
AU - Van Der Laken, Conny J.
N1 - Funding Information:
The authors gratefully acknowledge Mariska Verlaan and Ricardo Vos for their excellent technical support with the PET scans and animal experiments. Rolph van Kooij and Martien Mooijer are thanked for [18F]fluoro-PEG-folate tracer synthesis and planning. This study was supported by VU University Medical Center (Cancer Center Amsterdam) (CCA-PV13/87).
Publisher Copyright:
© 2018 Durga M. S. H. Chandrupatla et al.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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 [ 18 F]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. [ 18 F]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. [ 18 F]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 [ 18 F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.
AB - 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 [ 18 F]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. [ 18 F]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. [ 18 F]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 [ 18 F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.
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U2 - 10.1155/2018/8092781
DO - 10.1155/2018/8092781
M3 - Article
C2 - 29681783
AN - SCOPUS:85043495460
VL - 2018
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
SN - 1555-4309
M1 - 8092781
ER -