Quantifying disease activity in rheumatoid arthritis with the TSPO PET ligand 18F-GE-180 and comparison with 18F-FDG and DCE-MRI

被引:14
作者
De Groot, Marius [1 ,2 ]
Patel, Neel [1 ]
Manavaki, Roido [2 ]
Janiczek, Robert L. [1 ]
Bergstrom, Mats [1 ]
Ostor, Andrew [3 ]
Gerlag, Danielle [4 ]
Roberts, Alexandra [1 ]
Graves, Martin J. [2 ]
Karkera, Yakshitha [5 ]
Fernando, Disala [6 ]
Mistry, Prafull [5 ]
Walker, Adam [6 ]
Wisniacki, Nicolas [1 ]
Fryer, Tim D. [7 ]
Jimenez-Royo, Pilar [1 ]
机构
[1] GlaxoSmithKline R&D, Clin Pharmacol & Expt Med, Gunnels Wood Rd, Stevenage, Herts, England
[2] Univ Cambridge, Dept Radiol, Cambridge, England
[3] Monash Univ, Cabrini Med Ctr, Melbourne, Vic, Australia
[4] RxCelerate, Cambridge, England
[5] GlaxoSmithKline R&D, Biostat, Bangalore, Karnataka, India
[6] Addenbrookes Hosp, GlaxoSmithKline R&D, CUC, Cambridge, England
[7] Univ Cambridge, Wolfson Brain Imaging Ctr, Dept Clin Neurosci, Cambridge, England
关键词
PET; TSPO; FDG; MRI; Rheumatoid arthritis; POSITRON-EMISSION-TOMOGRAPHY; TRANSLOCATOR PROTEIN; MAGNETIC-RESONANCE; FDG-PET; MICROGLIAL ACTIVATION; SYNOVITIS; INFLAMMATION; MACROPHAGE; MODEL; C-11-(R)-PK11195;
D O I
10.1186/s13550-019-0576-8
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using F-18-fluorodeoxyglucose (F-18-FDG) or tracers targeting the translocator protein (TSPO). To evaluate F-18-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared F-18-GE-180 uptake with that of F-18-FDG and DCE-MRI measures of inflammation. Methods Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with F-18-GE-180 and F-18-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUVmax). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient K-trans using Pearson correlation (r). Results PET/CT imaging with F-18-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). F-18-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09-0.31). F-18-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUVmax vs. K-trans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). Conclusions The correlations between DCE-MRI parameters and F-18-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer F-18-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.
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