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

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 mon...

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Autores principales: Chandrupatla, Durga M. S. H., Jansen, Gerrit, Mantel, Elise, Low, Philip S., Matsuyama, Takami, Musters, René P., Windhorst, Albert D., Lammertsma, Adriaan A., Molthoff, Carla F. M., van der Laken, Conny J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841060/
https://www.ncbi.nlm.nih.gov/pubmed/29681783
http://dx.doi.org/10.1155/2018/8092781
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author Chandrupatla, Durga M. S. H.
Jansen, Gerrit
Mantel, Elise
Low, Philip S.
Matsuyama, Takami
Musters, René P.
Windhorst, Albert D.
Lammertsma, Adriaan A.
Molthoff, Carla F. M.
van der Laken, Conny J.
author_facet Chandrupatla, Durga M. S. H.
Jansen, Gerrit
Mantel, Elise
Low, Philip S.
Matsuyama, Takami
Musters, René P.
Windhorst, Albert D.
Lammertsma, Adriaan A.
Molthoff, Carla F. M.
van der Laken, Conny J.
author_sort Chandrupatla, Durga M. S. H.
collection PubMed
description 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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spelling pubmed-58410602018-04-21 Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate Chandrupatla, Durga M. S. H. Jansen, Gerrit Mantel, Elise Low, Philip S. Matsuyama, Takami Musters, René P. Windhorst, Albert D. Lammertsma, Adriaan A. Molthoff, Carla F. M. van der Laken, Conny J. Contrast Media Mol Imaging Research Article 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. Hindawi 2018-02-21 /pmc/articles/PMC5841060/ /pubmed/29681783 http://dx.doi.org/10.1155/2018/8092781 Text en Copyright © 2018 Durga M. S. H. Chandrupatla et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chandrupatla, Durga M. S. H.
Jansen, Gerrit
Mantel, Elise
Low, Philip S.
Matsuyama, Takami
Musters, René P.
Windhorst, Albert D.
Lammertsma, Adriaan A.
Molthoff, Carla F. M.
van der Laken, Conny J.
Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title_full Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title_fullStr Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title_full_unstemmed Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title_short Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [(18)F]Fluoro-PEG-Folate
title_sort imaging and methotrexate response monitoring of systemic inflammation in arthritic rats employing the macrophage pet tracer [(18)f]fluoro-peg-folate
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841060/
https://www.ncbi.nlm.nih.gov/pubmed/29681783
http://dx.doi.org/10.1155/2018/8092781
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