HomeCirculation: Cardiovascular ImagingVol. 13, No. 6Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBNovel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging Jason M. Tarkin, MD, PhD, Christopher Wall, MD, Deepa Gopalan, MD, Luigi Aloj, MD, Roido Manavaki, PhD, Tim D. Fryer, PhD, Eric O. Aboagye, MD, PhD, Martin R. Bennett, MD, PhD, James E. Peters, MD, PhD, James H.F. Rudd, MD, PhD and Justin C. Mason, MD, PhD Jason M. TarkinJason M. Tarkin Jason M. Tarkin, MD, PhD, Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Hill’s Rd, Box 110, Cambridge CB2 0QQ, United Kingdom. Email E-mail Address: [email protected] https://orcid.org/0000-0002-9132-120X Division of Cardiovascular Medicine (J.M.T., C.W., M.R.B., J.H.F.R.), University of Cambridge, United Kingdom. Vascular Sciences, National Heart and Lung Institute (J.M.T., J.C.M.), Imperial College London, United Kingdom. Search for more papers by this author , Christopher WallChristopher Wall Division of Cardiovascular Medicine (J.M.T., C.W., M.R.B., J.H.F.R.), University of Cambridge, United Kingdom. Search for more papers by this author , Deepa GopalanDeepa Gopalan Department of Radiology, Cambridge University Hospitals NHS Trust, United Kingdom (D.G.). Search for more papers by this author , Luigi AlojLuigi Aloj Department of Radiology (L.A., R.M.), University of Cambridge, United Kingdom. Search for more papers by this author , Roido ManavakiRoido Manavaki Department of Radiology (L.A., R.M.), University of Cambridge, United Kingdom. Search for more papers by this author , Tim D. FryerTim D. Fryer Department of Clinical Neurosciences (T.D.F.), University of Cambridge, United Kingdom. Search for more papers by this author , Eric O. AboagyeEric O. Aboagye Department of Surgery and Cancer (E.O.A.), Imperial College London, United Kingdom. Search for more papers by this author , Martin R. BennettMartin R. Bennett Division of Cardiovascular Medicine (J.M.T., C.W., M.R.B., J.H.F.R.), University of Cambridge, United Kingdom. Search for more papers by this author , James E. PetersJames E. Peters Department of Immunology and Inflammation (J.E.P.), Imperial College London, United Kingdom. Health Data Research UK (J.E.P.). Search for more papers by this author , James H.F. RuddJames H.F. Rudd Division of Cardiovascular Medicine (J.M.T., C.W., M.R.B., J.H.F.R.), University of Cambridge, United Kingdom. Search for more papers by this author and Justin C. MasonJustin C. Mason Vascular Sciences, National Heart and Lung Institute (J.M.T., J.C.M.), Imperial College London, United Kingdom. Search for more papers by this author Originally published28 May 2020https://doi.org/10.1161/CIRCIMAGING.119.010389Circulation: Cardiovascular Imaging. 2020;13:e010389Although 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an important diagnostic test for Takayasu arteritis (TAK),118F-FDG lacks inflammatory cell selectivity and cannot accurately distinguish arteritis from metabolically active vascular remodeling.2 This observation has led to the search for more sensitive and specific PET tracers for TAK. Macrophage activation antigen SST2 (somatostatin receptor subtype-2) PET represents a potential alternative imaging biomarker for defining disease activity in TAK, as macrophages are a major feature of the inflammatory infiltrate. We aimed to determine the ability of SST2 PET/magnetic resonance imaging (MRI) to detect arteritis in 2 patients with clinically active TAK.Case 1A 47-year-old woman with a 20-year history of TAK presented with recurrent chest pain, arthralgia, and carotidynia for the past 5 months. Immunosuppressive therapy had been gradually weaned off 10 months earlier following long-standing remission. Prior investigations had identified diffuse left subclavian and mild right carotid arterial stenoses (Figure 1A), a nonobstructive ostial right coronary artery lesion, and moderate aortic regurgitation with normal aortic root dimensions and left ventricular function. Examination revealed a chronically reduced left radial pulse and a right carotid bruit. Blood pressure in the right arm was 130/80 mm Hg and in the left, 120/70 mm Hg. CRP (C-reactive protein) was raised at 31.6 mg/L (normal range, <5.0) and erythrocyte sedimentation rate, 67 mm/h (normal range, 1–19). Indian Takayasu Activity Score-A was 7 and National Institutes of Health score, 3, indicating clinically active TAK. 18F-FDG PET confirmed active TAK with increased tracer uptake in the ascending aorta (Figure 1C and 1F). MRI showed no evidence of progressive arterial injury.Download figureDownload PowerPointFigure 1. Relapsing Takayasu arteritis. Case 1: Magnetic resonance imaging (MRI) showing (A) left subclavian (solid arrow) and proximal right carotid (dashed arrow) arterial stenoses and (D) periaortic thickening (arrowhead); (B and E) 68Ga-DOTA-(Tyr3)-octreotate (DOTATATE) positron emission tomography (PET)/MRI and (C and F) 18F-fluorodeoxyglucose (18F-FDG) PET images in coronal (top) and axial (bottom) views demonstrating avid tracer signal (asterisks) in the ascending aorta.Despite treatment with depo-methylprednisolone 160 mg and azathioprine 150 mg daily, she remained symptomatic 5 months later, with elevated CRP (17.5 mg/L) and erythrocyte sedimentation rate (32 mm/h). Vascular PET/MRI was performed as part of ongoing research study NCT04071691, using the SST2 tracer 68Ga-DOTA-(Tyr3)-octreotate (DOTATATE) and a GE SIGNA PET/MRI scanner. Images acquired 50 minutes after an injected activity of 234 MBq in two 30-minute bed positions covering the upper body were reconstructed with standard corrections applied. There was circumferential periaortic thickening in the ascending aorta on T1-weighted black blood MRI (Figure 1D) and corresponding avid SST2 PET signal (Figure 1B and 1E) with a maximum standardized uptake value (SUVmax) in the aorta of 3.1 and maximum tissue-to-blood (TBRmax) ratio of 5.6. The pattern of aortic 68Ga-DOTATATE binding was near identical to that seen on the prior 18F-FDG imaging.Case 2A 29-year-old woman reported severe fatigue and episodes of sweating. A diagnosis of TAK had been made 2 years earlier based on constitutional symptoms and raised inflammatory markers, with periaortic thickening on computed tomographic scanning and low-level aortic 18F-FDG uptake on PET scanning 2 weeks after initiation of high-dose prednisolone. She continued azathioprine 150 mg daily and low-dose prednisolone maintenance therapy. On examination, pulses were present and symmetrical and blood pressure, 90/60 mm Hg. She had clinically active disease (CRP, 21.5 mg/L; erythrocyte sedimentation rate, 60 mm/h; Indian Takayasu Activity Score-A score, 9; and National Institutes of Health score, 2). While previous MRI showed left subclavian and right vertebral artery stenoses (Figure 2A), there was no progressive arterial injury on repeat scanning despite active disease.Download figureDownload PowerPointFigure 2. Treatment-refractory Takayasu arteritis. Case 2: Magnetic resonance imaging (MRI) showing (A) left subclavian artery stenosis (solid arrow) and (C) thickening of the major branches of the aortic arch (dashed arrows); 18F-fluoroethyl triazole [Tyr3] octreotate (FET-βAG-TOCA) positron emission tomography/MRI in (B) coronal and (D) axial views demonstrating increased tracer uptake (asterisks) in the affected arteries.Therapy was switched to prednisolone 20 mg once daily and methotrexate 20 mg once weekly. However, disease activity persisted with a further increase in CRP (39.6 mg/L) and erythrocyte sedimentation rate (106 mm/h). Vascular PET/MRI was performed using another SST2 tracer, 18F-fluoroethyl triazole [Tyr3] octreotate (FET-βAG-TOCA) with an injected activity of 244.1 MBq. The major branches of the aortic arch were thickened on MRI (Figure 2C), with a striking pattern of increased PET signals identified in the brachiocephalic trunk, left common carotid, and bilateral subclavian arteries (Figure 2B and 2D). The maximum vascular SST2 PET signal (SUVmax, 1.9; TBRmax, 3.5) was in the proximal left common carotid artery. Treatment was subsequently escalated to tocilizumab with good effect.TAK is a granulomatous large-vessel vasculitis that typically affects young women, resulting in arterial stenoses, aneurysms, and occlusions. While 18F-FDG PET is useful for diagnosing TAK,1 it has more limited value for tracking therapeutic responses or detecting residual arteritis and the risk of progressive arterial injury, highlighting a need for more precisely targeted PET tracers.2 We have previously shown the ability of SST2 PET imaging using 68Ga-DOTATATE for marking high-risk atherosclerotic plaques.4 In these first 2 cases of SST2 PET/MRI in large-vessel vasculitis, arteritis was accurately identified, suggesting this novel approach merits further evaluation. AcknowledgmentsDr Tarkin is supported by a Wellcome Trust Clinical Research Career Development Fellowship (211100/Z/18/Z) and the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC). Dr Manavaki is supported by the NIHR Camrbdige BRC. Prof Bennett is supported by the British Heart Foundation. Dr Peters is supported by a United Kingdom Research and Innovation Innovation Fellowship at Health Data Research UK (MR/S004068/). Dr Rudd is part supported by the NIHR Cambridge BRC, the British Heart Foundation, the Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council, and the Wellcome Trust. Profs Aboagye and Mason acknowledge support from the NIHR Imperial BRC.Sources of FundingThis study was supported by the Wellcome Trust, NIHR Imperial BRC.DisclosuresNone.FootnotesJason M. Tarkin, MD, PhD, Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Hill’s Rd, Box 110, Cambridge CB2 0QQ, United Kingdom. Email [email protected]ac.uk