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FRI0041 In vivo monitoring of anti-folate therapy in arthritic rats using [18f]fluoro-peg-folate and pet
  1. DMSH Chandrupatla1,
  2. CJ van der Laken1,
  3. R Vos2,
  4. M Verlaan2,
  5. R van Kooij2,
  6. AD Windhorst2,
  7. Q Chen3,
  8. PS Low3,
  9. AA Lammertsma2,
  10. G Jansen1,
  11. CFM Molthoff2
  1. 1Amsterdam Rheumatology and immunology Centre – location VUmc
  2. 2Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands
  3. 3Department of Chemistry, Purdue University, West Lafayette, United States

Abstract

Background Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA). The folate receptor β (FR-β) is expressed on these macrophages [1] and [18F]fluoro-PEG-folate positron emission tomography ([18F]fluoro-PEG-folate PET) can be used to visualize arthritis in vivo [2]. In addition, [18F]fluoro-PEG-folate PET could be a highly interesting tool for therapeutic monitoring of MTX therapy, the corner stone for RA therapy.

Objectives To study the potential of [18F]fluoro-PEG-folate PET for monitoring response to MTX in a rat model of RA.

Methods Arthritic rats [3] (n=3–6 per group) received interventions with either MTX [i.p., 1mg/kg; 2 times (group A) or 4 times (group B)] or PBS (control group)] with a time interval of 3–4 days. Healthy rats didn't receive any arthritic induction or MTX therapy. [18F]fluoro-PEG-folate PET-CT were acquired for one hour after tracer injection [2]. Scans were analysed using the region of interest method and standardized uptake values (SUVs) were determined (50–60 min time frame). Sixty minutes after the PET scan, ex-vivo tissue distribution was performed and the amount of radioactivity measured in a gamma counter (expressed as percentage of the injected dose/gram tissue (%ID/g)) [2]. For histopathology (Haematoxylin-Eosin (HE) and immunohistochemistry with macrophage specific antibodies ED1 (∼CD68) and ED2 (∼CD163) were applied. Synovial macrophages were counted in predefined areas of the knees [3].

Results PET scans clearly visualized significantly lower SUVs (1.5-fold, p<0.01) in arthritic knees of both MTX-treated groups, approximating the levels observed in healthy rats. Corroborating [18F]fluoro-PEG-folate PET, ex vivo tissue distribution [18F]fluoro-PEG-folate demonstrating a 2- and 4-fold decrease (group A and B, respectively) in tracer uptake in arthritic knees after MTX therapy (0.12 and 0.06 for groups A and B, and 0.22%ID/g for controls, respectively) (Figure). This reduction in uptake of [18F]fluoro-PEG-folate in arthritic knees was also associated with a significant decrease in ED1 and ED2 positive synovial macrophages in arthritic knees (∼4 fold) for both treated groups compared with control rats knees (p<0.01).

Conclusions This study in arthritic rats underscores the potential and usefulness of [18F]fluoro-PEG-folate PET as tool to monitor of MTX therapy and potentially other anti-folate treatments of RA.

References

  1. Van der Heijden et al, Arthr & Rheum (2009).

  2. Gent et al, Arthr Res Ther (2013).

  3. Chandrupatla et al, BioMed Res Int (2015).

References

Disclosure of Interest None declared

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