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

Durga M.S.H. Chandrupatla; Gerrit Jansen; Elise Mantel; Philip S. Low; Takami Matsuyama; René P. Musters; Albert D. Windhorst; Adriaan A. Lammertsma; Carla F.M. Molthoff; Conny J. Van Der Laken

doi:10.1155/2018/8092781

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

Durga M.S.H. Chandrupatla, Gerrit Jansen, Elise Mantel, Philip S. Low, Takami Matsuyama, René P. Musters, Albert D. Windhorst, Adriaan A. Lammertsma, Carla F.M. Molthoff, Conny J. Van Der Laken

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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 (FR β), 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 FR β 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, FR β-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.

Original language	English (US)
Article number	8092781
Pages (from-to)	8092781
Journal	Contrast Media and Molecular Imaging
Volume	2018
DOIs	https://doi.org/10.1155/2018/8092781
State	Published - 2018

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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Chandrupatla, D. M. S. H., Jansen, G., Mantel, E., Low, P. S., Matsuyama, T., Musters, R. P., Windhorst, A. D., Lammertsma, A. A., Molthoff, C. F. M., & Van Der Laken, C. J. (2018). Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [ ¹⁸ F]Fluoro-PEG-Folate. Contrast Media and Molecular Imaging, 2018, 8092781. Article 8092781. https://doi.org/10.1155/2018/8092781

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 et al.
In: Contrast Media and Molecular Imaging, Vol. 2018, 8092781, 2018, p. 8092781.

Research output: Contribution to journal › Article › peer-review

Chandrupatla, DMSH, Jansen, G, Mantel, E, Low, PS, Matsuyama, T, Musters, RP, Windhorst, AD, Lammertsma, AA, Molthoff, CFM & Van Der Laken, CJ 2018, 'Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [ ¹⁸ F]Fluoro-PEG-Folate', Contrast Media and Molecular Imaging, vol. 2018, 8092781, pp. 8092781. https://doi.org/10.1155/2018/8092781

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

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 (FR β), 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 FR β 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, FR β-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. ",

author = "Chandrupatla, \{Durga M.S.H.\} and Gerrit Jansen and Elise Mantel and Low, \{Philip S.\} and Takami Matsuyama and Musters, \{Ren{\'e} P.\} and Windhorst, \{Albert D.\} and Lammertsma, \{Adriaan A.\} and Molthoff, \{Carla F.M.\} and \{Van Der Laken\}, \{Conny J.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Durga M. S. H. Chandrupatla et al.",

year = "2018",

doi = "10.1155/2018/8092781",

language = "English (US)",

volume = "2018",

pages = "8092781",

journal = "Contrast Media and Molecular Imaging",

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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.

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 [ 18F]fluoro-PEG-folate, targeting folate receptor β (FR β), 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 FR β 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, FR β-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.

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 [ 18F]fluoro-PEG-folate, targeting folate receptor β (FR β), 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 FR β 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, FR β-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.

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U2 - 10.1155/2018/8092781

DO - 10.1155/2018/8092781

M3 - Article

C2 - 29681783

AN - SCOPUS:85043495460

SN - 1555-4309

VL - 2018

SP - 8092781

JO - Contrast Media and Molecular Imaging

JF - Contrast Media and Molecular Imaging

M1 - 8092781

ER -

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

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