Pos0159 [18f]-Peg-Folate Pet/Ct Guidance for Synovial Pathotype Differentiation in Rheumatoid Arthritis: A Pilot/Exploratory Study

Background: The use of biologics has significantly improved the therapy of rheumatoid arthritis, however, approximately 30% of patients remain clinically active regardless of the therapy [1]. Synovial pathotypes, determined by the immune cell subtypes, can guide treatment decisions by targeting specific cell populations in inflamed tissue [2]. However, pathotyping requires invasive synovial biopsy assessment. Molecular imaging of macrophages using positron emission tomography (PET) is a promising non-invasive tool for evaluating and quantifying disease activity and predicting treatment responses in RA patients [3]. The use of [¹⁸F]-PEG-Folate, a folate receptor beta-targeted radiotracer, offers a unique opportunity to visualize and quantify synovial macrophages, reflecting RA disease activity [4]. Therefore the technique may allow the differentiation of myeloid from non-myeloid synovial subtypes to guide RA management. Objectives: To explore the potential of quantitative [¹⁸F]-PEG-Folate PET as a non-invasive method to guide differentiation of synovial pathotypes as a readout to predict response to biological treatments in RA. Methods: [¹⁸F]-PEG-Folate scans were performed in clinically active RA patients with two or more active joints including at least 1 knee or ankle joint accessible for synovial tissue biopsy. Synovial tissue biopsies were collected from the most inflamed joints (knees or ankles). Immune cell infiltrates positive for CD3, CD20, CD138, and CD68 were investigated with immunohistochemistry staining (IHC) to examine the synovial pathotype. PET/CT scans were quantitatively analyzed using Vivo-quant software. Synovial tissue regions of interest (ROIs) were delineated on PET/CT per individual joint in PET-positive knees and ankles. Standardized uptake values (SUVs) of peak region normalized for body weight were calculated in these ROIs to determine quantitative tracer uptake per joint. SUV values in joints were compared to synovial pathotypes of tissue excised from the same joints (descriptive analysis). Results: [¹⁸F]-PEG-Folate PET scans depicted RA disease activity in multiple joints of n=7 clinically active RA patients, including synovial inflammation in at least one knee or ankle joint per patient that was subjected to arthroscopic excision of synovial tissue. Based on synovial tissue IHC, joints of n=4 patients matched the diffuse-myeloid pathotype, of n=2 patients the fibroid/pauci-immune, and of n=1 patient the lymphoid myeloid pathotype [2]. Mean SUV of knee and/or ankle joints on [¹⁸F]-PEG-Folate PET/CT were up to 6 times lower when excised synovial tissue was identified as fibroid/pauci-immune pathotype. (Figure 1A–C) Conclusion: This first explorative analysis demonstrates that quantitative macrophage [¹⁸F]-PEG-Folate PET/CT shows promise for non-invasive differentiation of synovial pathotypes, with myeloid subtypes showing higher folate targeting than joints with the pauci-immune pathotype. These data can be the base for further investigation of [¹⁸F]-PEG-Folate PET/CT for treatment stratification. REFERENCES: [1] MJ Tornero et al., J Clin Med. 2023;13:48. [2] F Humby et al., Ann Rheum Dis. 2019;78(6):761-772. [3] NJF Verweij et al., RMD Open. 2022 Feb;8(1):e002108. [4] NJF Verweij et al., Sci Rep. 2020 Jan 23;10(1):1047. Acknowledgements: Tanja Konijn, MCBI, Amsterdam University Medical Center,, location VUmc, Amsterdam, The Netherlands. Disclosure of Interests: Aiarpi Ezdoglian Biocad, GlaxoSmithKline, Wouter van Binsbergen: None declared, Wouter R.P. van der Heijden: None declared, Maarten M. Steinz: None declared, Marleen G.H. van de Sande: None declared, Arthur Kievit: None declared, Myrthe den Toom: None declared, Sander W. Tas GlaxoSmithKline, Jan Piet Van Hamburg: None declared, Gerrit Jansen: None declared, Conny J. van der Laken Novartis, Pfizer, Abbvie, UCB, Bristol Myers Squibb, GlaxoSmithKline, Galapagos, Novartis, Pfizer, Abbvie, UCB, Bristol Myers Squibb, GlaxoSmithKline, Galapagos.