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

Contrast Media Mol Imaging. 2018 Feb 21;2018:8092781. doi: 10.1155/2018/8092781. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental* / chemically induced
  • Arthritis, Experimental* / diagnostic imaging
  • Arthritis, Experimental* / metabolism
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / diagnostic imaging
  • Arthritis, Rheumatoid* / metabolism
  • Fluorine Radioisotopes / pharmacology*
  • Folic Acid / analogs & derivatives*
  • Folic Acid / pharmacology
  • Inflammation / chemically induced
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Macrophages / metabolism
  • Macrophages / pathology
  • Methotrexate / pharmacokinetics
  • Methotrexate / pharmacology*
  • Polyethylene Glycols / pharmacology*
  • Positron-Emission Tomography*
  • Rats
  • Rats, Wistar


  • Fluorine Radioisotopes
  • poly(ethylene glycol)-folate
  • Polyethylene Glycols
  • Folic Acid
  • Fluorine-18
  • Methotrexate