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Background:One of the main characteristics of rheumatoid arthritis (RA) is angiogenesis, which is linked to both the disease’s activity and duration. Two key proteins, vimentin and αvβ3 integrin, are critically involved in angiogenesis in RA. As a result, both may be used as diagnostic candidates for early detection and precise RA treatment. Positron emission tomography (PET) scans using radiotracers for αvβ3 and vimentin may provide non-invasive monitoring of angiogenesis which is currently being investigated in a rat model of arthritis.Objectives:To investigate the potential of integrin and vimentin as targets for molecular imaging of angiogenesis in RA in a preclinical Antigen-Induced Arthritis (AIA) rat model of arthritis.Methods:AIA rats’ knee tissues were examined using immunohistochemical (IHC) staining to determine the expression of vimentin and integrin αvβ3. For both targets we have PET tracers available. In the AIA model, following systemic immunization by injecting a mixture of methylated bovine serum albumin (mBSA) in complete Freund’s adjuvant (CFA) and a customized Bordetella pertussis (CBP) antigen, arthritis is induced in one knee with the contralateral knee serving as control [1]. QuPath software was used to analyze stained sections from AIA and their contralateral control knees, and healthy rat knees (mean ± SEM). In addition to IHC, we investigated the inhibitory effects of microdose Fluciclatide, a small synthetic cyclic peptide that has a high affinity for integrins αvβ3/5. This was performed in a 3D spheroid angiogenesis model [2]. Statistical analysis involved one-way ANOVA for all experiments (n=3-6).Results:In arthritic knee tissues, vimentin expression was markedly and significantly increased in arthritic compared to both control and normal knees (6.5 and 7.5 fold respectively, p≤ 0.001) (Figure 1A). Additionally, αvβ3 expression was elevated in arthritic knees compared to normal rat knees (3.7-fold, p<0.05), and contralateral knees (2.6-fold), however this difference did not achieve statistical significance (Figure 1B). With demonstrated efficacy in cancer imaging research, [18F]-Fluciclatide has potential in RA imaging as well. The 3D spheroid angiogenesis model demonstrated that Fluciclatide at microdoses ≤ 0.5 μM does not exhibit inhibitory biologic effects, making it a viable agent for in vivo imaging (Figure 2).Conclusion:The current study shows that the AIA model is suitable to study novel PET tracers targeting both vimentin and integrin αvβ3 for angiogenesis imaging in arthritis. Moreover, markedly increased vimentin and integrin αvβ3 expression in arthritic knees underscores aberrant angiogenesis that provide valuable insights into arthritis pathology. Ongoing PET imaging with [18F]-Fluciclatide for αvβ3 [3] and 89Zr-anti-vimentin nanobodies [4] holds promise for precise visualization and assessment of angiogenesis in RA.REFERENCES:[1] Chandrupatla DM, et al. Biomed Res Int. 2015;2015:509295.[2] Maracle, C.X., et al. Rheumatology (Oxford). 2017;56(2):294-302.[3] Battle, M.R., et al. J Nucl Med. 2011;52(3):424-430.[4] van Beijnum, J.R., et al. Nat Commun. 2022;13(1):2842.Figure 1.IHC staining of vimentin (A) and integrin αvβ3 (B) in AIA and healthy rats knee tissues. The scale bars represent 200 μm for the reference images and 100 μm for the magnified images. Quantitative analysis of stained sections from AIA knees, their respective control knees, as well as healthy rat knees was conducted using QuPath software by training object classifier for recognizing positive cells. The data is presented as mean ± SEM for AIA rats (n=6) and normal rats (n=5). (**p≤ 0.001, *p< 0.05, ns:not significant)Figure 2.Representative confocal pictures (10X) of the 3D spheroid-based model of angiogenesis composed of endothelial cells (EC) (cyan) and normal human dermal fibroblasts (NHDF) (magenta) and impact of microdosing of Fluciclatide on sprouting. Cell tracker dyes was used to monitor cells. Significant induction of sprouting was observed following stimulation with the growth factors VEGF/bFGF. Data represents Mean ± SEM of 3 independent experiments. All the scale bars are 200 μm. (* p<0.05, ns: not significant)REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:There is insufficient knowledge about the usefulness and methodology of using a whole body positron emission tomography (PET) tracer such as F18-fluordeoxyglucose ([18F]-FDG) for assessment of muscle pathology in rheumatic musculoskeletal diseases (RMDs). In RMDs, characterised by affected joints, a common symptom such as muscle weakness is shown to be associated with altered muscle glucose metabolism [1]. [18F]-FDG PET can be used to visualise the altered glucose metabolism in muscles which allows for a non-invasive investigation of changes in muscle metabolism of the whole body and at the cellular level [2]. Consequently, leading to more personalised interventions of weakened muscles.Objectives:The objectives were to determine the most appropriate methodology to assess [18F]-FDG muscular uptake in RMDs and to compare muscular uptake between patients with rheumatoid arthritis (RA), osteoarthritis (OA), inflammatory idiopathic myopathy (IIM), and controls.Methods:Whole body [18F]-FDG PET scans were retrospectively analyzed for muscular tracer uptake. The deltoid; biceps brachii; triceps brachii; psoas; quadriceps and; hamstrings were evaluated in 31 RMDs (11 RA, 10 OA, 10 IIM) and eight control persons. For the qualitative assessment, regions with positive uptake and the uptake pattern were recorded. Two methods were compared to quantitatively assess [18F]-FDG uptake in the muscles: fixed volume of interest (VOI) (fixed height position on the bone) and hotspot VOI (visually highest uptake determined qualitatively), whereafter standardized uptake values (SUVs) were compared for different muscle groups between the RMDs and controls.Results:[18F]-FDG PET enables qualitative and quantitative assessment of muscle glucose uptake in RA, OA and IIM patients. Differences in [18F]-FDG muscle uptake between the RMDs were observed in this study. Qualitative assessment: [18F]-FDG uptake was observed in all muscle groups of OA, RA and IIM patients. A heterogenous uptake pattern of [18F]-FDG was mostly seen in the quadriceps and the hamstring muscles whereas, in the other muscle groups, the uptake pattern varied between heterogenous and homogenous. Quantitative assessment: SUVs of FDG uptake either assessed by fixed or hospot VOI method were highly associated with each other (R2=0.9, p<0.0001). However, the hotspot VOI method was preferred due to its higher sensitivity to detect differential [18F]-FDG muscle uptake as depicted by the Bland-Altman plot (mean=0.147, 95% CI [-0.411, 0.117]). In all muscle groups, the IIM patients had the highest uptake followed by the OA and RA patients, respectively. The muscles that were the most affected in the RMDs were the biceps brachii, deltoids and the quadriceps. Compared to the controls, the RA, OA and IIM patients had a 1.43, 1.46 and 2.43 uptake in the biceps brachii, respectively; a 1.14, 1.30 and 1.99 higher uptake in the deltoids, respectively and; a 1.35, 1.63 and 2.09 higher uptake in quadriceps, respectively.Conclusion:[18F]-FDG PET enables qualitative and quantitative assessment, and differentiation of muscle glucose uptake in RA, OA and IIM patients both at the muscle level and at the patient group level. The hotspot method and the SUVpeak measurement are recommended to quantitatively identify differential uptake between RA, OA, IIM patients and controls. Remarkably, FDG uptake was increased in several muscle groups in all studied RMDs as compared to controls, pointing at altered glucose metaolism in muscles of these RMDsThis study provides the evidence for future exploration of using [18F]-FDG PET to study muscle pathology in RMDs.REFERENCES:[1] Vaamonde-García C, López-Armada MJ. Role of mitochondrial dysfunction on rheumatic diseases. Biochem Pharmacol. 2019;165:181-195. DOI:10.1016/j.bcp.2019.03.008.[2] Vaidyanathan S, Patel CN, Scarsbrook AF, Chowdhury FU. FDG PET/CT in infection and inflammation--current and emerging clinical applications. Clin Radiol. 2015;70(7):787-800. DOI:10.1016/j.crad.2015.03.010.Acknowledgements:NIL.Disclosure of Interests:None declared.

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)Figure 1.Examples of [18F]-PEG-Folate PET/CT images with corresponding immunohistochemistry data. (A) Representative [18F]-PEG-Folate PET/CT images of affected joints; (B) Synovial pathotypes and IHC images of immune cell infiltration in the corresponding joints; (C) Mean SUV values of [18F]-PEG-Folate PET positive joints expressed for the different synovial pathotypes;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.

Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial inflammation and infiltration of various immune cells, including macrophages. Novel whole-body molecular imaging with positron emission tomography (PET) and the use of specific PET tracers can non-invasively detect and quantify the presence of macrophages in the RA inflamed synovium, as read-out of RA disease activity. The mannose receptor (CD206) is a macrophage C-lectin surface receptor suitable for molecular-imaging of macrophages, however its value for PET-imaging in the context of RA remains to be established. Moreover, recently three distinct pathotypes of RA have been identified: fibroid-pauci (FP) immune (fibroblast-rich), diffuse-myeloid (DM, macrophage-rich) and lympho-myeloid (LM, lymphocyte- and macrophage rich) pathotype [1, 2] which may differentially express CD206 as base for PET stratification of RA subgroupsObjectives:(1) Investigate the expression of CD206 in the three different RA pathotypes on human synovial tissue of RA patients. (2) Establish if a novel nanobody (sdAb) PET tracer targeting CD206, i.e. [68Ga]Ga-NOTA-MMR-sdAb, is suitable for PET imaging of macrophages in an animal model of RA.Methods:Immunofluorescence (IF) analysis of CD206 expression was performed in ankle or knee biopsies of inflamed synovium from RA patients with a fibroid-pauci immune (N=9), diffuse-myeloid (N=8) and lympho-myeloid pathotype (N=8). The expression in all RA pathotypes was compared to expression of pan-macrophage marker CD68. PET scans (Mediso nanoPET/CT scanner) with 10 μg, ~15 MBq [68Ga]Ga-NOTA-MMR-sdAb were performed in antigen-induced arthritic (AIA) rats [3] (N=4). [68Ga]Ga-NOTA-MMR-sdAb was synthesized (>95% radiochemical purity and high molar activity) as described before [4]. PET imaging results were validated by immunohistochemistry (IHC) for macrophage receptor CD68 (a pan-macrophage marker) and CD206 in AIA knee tissues (N=8).Results:In synovial tissue of RA patients, average expression of CD206 was significantly increased in the DM and LM compared to the FP immunopathotype (respectively 3.4- and 1.7-fold ** p<0.01) (Figure 1A and B). Quantitative CD206 expression was highest in the DM immunopathotype. Dynamic PET scanning in AIA rats, showed that the uptake of [68Ga]Ga-NOTA-MMR-sdAb in the arthritic knee was significantly higher (1.7-fold) than in the control knee from 2 min onwards after iv tracer injection (SUVmean arthritic 1.04 ± 0.08; SUVmean control 0.61 ± 0.06, p<0.001) (Figure 1C–E). IHC of CD68 and CD206 confirmed increased infiltration of macrophages in AIA arthritis-affected knees compared to the control knees (Figure 1F).Conclusion:The results of this study support the use of [68Ga]Ga-NOTA-MMR-sdAb for macrophage PET-imaging in RA joints, which should be further validated in (pre)clinical studies. Moreover, the human staining results indicate that CD206 may be used as a PET-imaging target to distinguish RA patients with a macrophage-rich pathotype vs. those with low or no macrophage infiltration. This may offer opportunities of baseline stratification of patients that most likely will or will not respond to macrophage targeting therapies.REFERENCES:[1] Pitzalis C, Kelly S, Humby F. New learnings on the pathophysiology of RA from synovial biopsies. Curr Opin Rheumatol. 2013;25(3):334-44.[2] Humby F, Lewis M, Ramamoorthi N, Hackney JA, Barnes MR, Bombardieri M, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Annals of the rheumatic diseases. 2019;78(6):761-72.[3] Chandrupatla DM, Weijers K, Gent YY, de Greeuw I, Lammertsma AA, Jansen G, et al. Sustained macrophage infiltration upon multiple intra-articular injections: an improved rat model of rheumatoid arthritis for PET guided therapy evaluation. Biomed Res Int. 2015;2015:509295.[4] Xavier C, Blykers A, Laoui D, Bolli E, Vaneyken I, Bridoux J, et al. Clinical Translation of [(68)Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages. Mol Imaging Biol. 2019;21(5):898-906.Acknowledgements:This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831514 (Immune-Image). The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.Disclosure of Interests:None declared.

BackgroundThree different synovial immunopathotypes of rheumatoid arthritis (RA) have been identified: Fibroid-Pauci immune (FP, fibroblast-rich), Diffuse-Myeloid (DM, macrophage-rich) and Lympho-Myeloid (LM, lymphocyte- and macrophage-rich), and have been associated with treatment outcome to biologicals [1]. Therefore, identification of the synovial immunopathotypes before the start of therapy could be supportive for development of individualized treatment strategies. However, this currently requires invasive synovial tissue sampling. Novel whole-body molecular imaging with positron emission tomography (PET) and the use of specific PET tracers can non-invasively detect and quantify the presence of immune cells in RA inflamed synovium. Folate-receptor beta (FRβ) is a cell surface receptor on macrophages, shown clinical exploitation for high specificity PET imaging of arthritis [2]. However, it remains to be elucidated whether FRβ is a suitable marker for RA immunopathotype stratification. Furthermore, it is unclear whether FRβ is expressed on macrophages with a pro-inflammatory (M1) or homeostatic (M2) phenotype in the 3 immunopathotypes.Objectives:(1) Investigate FRβ expression across the three distinct RA immunopathotypes.(2) Investigate FRβ expression in relation to the general macrophage marker CD68 and the mannose receptor CD206 (which is associated with M2-type macrophages [3]).MethodsSynovial biopsies of the RA-affected ankle or knee (N=28) were retrieved from RA patients with clinically active disease defined by ACR RA criteria [4]. Subsequently, biopsy sections were immunohistologically stained in order to stratify each patient into one of three RA-immunopathotypes. Confocal microscopy was used to determine CD68, FRβ and CD206 expression (integrated density), and co-expression (comparing fold-change average expression) for all patients within each immunopathotype (N=8-10/ group).ResultsOut of 28 RA synovial biopsies 10 could be classified as FP, 9 DM and 9 LM immunopathotype. Average expression of CD68, FRβ and CD206 was significantly increased in the DM and LM compared to the FP immunopathotype (## p<0.01). Quantitative CD68, FRβ and CD206 expression was highest in the DM immunopathotype. FRβ expression correlated significantly with CD206 expression in all three pathotypes (Spearman RFP= 0.67; RDM= 0.76; RLM= 0.49). On the contrary FRβ expression did not correlate with CD68 expression except in the DM pathotype (Spearman RDM= 0.46).ConclusionThe results of this study put forward that FRβ is a potential target for delineation of RA immunopathotypes, to be explored for non-invasive molecular imaging stratification. Furthermore, investigation of FRβ expression has an additive value over CD68 since it can be used to distinguish the presence of M2 macrophages in the RA synovium specifically.References[1] Lewis et al., Cell Rep. 2019;28(9):2455-2470.e5[2] Steinz et al., Front Immunol. 2022;13:819163[3] Alivernini et al., Nat. Med. 2020;26(8):1295-1306[4] Arnet et al., Arthritis Rheum. 1988;31(3):315-24Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation leading to joint damage and systemic complications. Angiogenesis promotes inflammation and contributes to RA progression. This study evaluated potential anti-angiogenic effects of several compounds including small-molecule kinase inhibitors, such as sunitinib (pan-kinase inhibitor), tofacitinib (JAK-inhibitor), NIKi (NF-κB-inducing kinase inhibitor), and the integrin-targeting peptide fluciclatide, using a scratch assay and 3D spheroid-based models of angiogenesis. For all drugs tested in the low micromolar range (1–25 μM), sunitinib (as positive anti-angiogenetic control) showed marked inhibition of endothelial cell (EC) migration and sprouting, effectively reducing both scratch closure and sprout formation. Tofacitinib exhibited marginal effectiveness in the scratch assay, but performed better in the 3D models (55% inhibition), whereas NIKi showed around 50% anti-angiogenic effects in both models. Fluciclatide changed EC morphology rather than migration, and only when stimulated with synovial fluid in spheroid model did it show inhibitory effects (at ≥2.5 µM), with none below this dosage. These results highlight the potential of NIKi and tofacitinib for angiogenesis inhibition and of fluciclatide for safe diagnostic targeting of microdose in RA, as well as the need for advanced screening models that mimic RA’s complex inflammatory pro-angiogenic environment.

Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([18F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [18F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [18F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [18F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [18F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [18F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [18F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland–Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [18F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [18F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [18F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUVpeak are recommended for quantitative assessment. High [18F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles.

Extensive angiogenesis is a characteristic feature in the synovial tissue of rheumatoid arthritis (RA) from a very early stage of the disease onward and constitutes a crucial event for the development of the proliferative synovium. This process is markedly intensified in patients with prolonged disease duration, high disease activity, disease severity, and significant inflammatory cell infiltration. Angiogenesis is therefore an interesting target for the development of new therapeutic approaches as well as disease monitoring strategies in RA. To this end, nuclear imaging modalities represent valuable non-invasive tools that can selectively target molecular markers of angiogenesis and accurately and quantitatively track molecular changes in multiple joints simultaneously. This systematic review summarizes the imaging markers used for single photon emission computed tomography (SPECT) and/or positron emission tomography (PET) approaches, targeting pathways and mediators involved in synovial neo-angiogenesis in RA.

Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([18F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [18F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [18F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [18F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [18F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [18F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [18F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland-Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [18F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [18F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [18F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUVpeak are recommended for quantitative assessment. High [18F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles.Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([18F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [18F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [18F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [18F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [18F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [18F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [18F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland-Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [18F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [18F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [18F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUVpeak are recommended for quantitative assessment. High [18F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles.