Arthritis Research & Therapy (May 2017)

In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography

  • Durga M. S. H. Chandrupatla,
  • Gerrit Jansen,
  • Ricardo Vos,
  • Mariska Verlaan,
  • Qingshou Chen,
  • Philip S. Low,
  • Albert D. Windhorst,
  • Adriaan A. Lammertsma,
  • Conny J. van der Laken,
  • Carla F. M. Molthoff

DOI
https://doi.org/10.1186/s13075-017-1325-x
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 9

Abstract

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Abstract Background Folate receptor β (FRβ) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRβ is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [18F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats. Methods Arthritic rats received either no treatment or MTX therapy (1 mg/kg, either 2× or 4×). Healthy rats did not receive any arthritic induction or therapy. [18F]fluoro-PEG-folate PET-CT scans (60 min) were performed before and after MTX therapy. Following PET, the ex-vivo tissue distribution of radioactivity was determined in excised knees and multiple tissues. Synovial macrophage infiltration in knee sections was quantified by immunohistochemistry using ED1 and ED2 antibodies. Results PET scans clearly visualized increased uptake of [18F]fluoro-PEG-folate in arthritic knees compared with contralateral knees. Significantly lower standard uptake values (1.5-fold, p < 0.01) were observed in arthritic knees of both MTX-treated groups after therapy, approximating the levels seen in healthy rats. Consistently, ex-vivo tissue distribution demonstrated a 2–4-fold lower tracer uptake in the arthritic knee of 2× and 4× MTX-treated rats, respectively, compared with control rats. These results were corroborated with significantly reduced (2–4-fold, p < 0.01) ED1-positive and ED2-positive synovial macrophages in arthritic knees of the MTX-treated rats compared with those of the control rats. Conclusion This study in arthritic rats underscores the potential and usefulness of [18F]fluoro-PEG-folate PET as a therapeutic monitoring tool of MTX therapy and potentially other anti-folate treatment of arthritis.

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