Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers


Autoři: S. T. G. Bruijnen aff001;  N. J. F. Verweij aff001;  Y. Y. J. Gent aff001;  M. C. Huisman aff002;  A. D. Windhorst aff002;  M. Kassiou aff003;  P. M. van de Ven aff004;  A. A. Lammertsma aff002;  O. S. Hoekstra aff002;  A. E. Voskuyl aff001;  C. J. van der Laken aff001
Působiště autorů: Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam UMC| location VUmc, Amsterdam, the Netherlands aff001;  Department of Radiology & Nuclear Medicine, Amsterdam UMC| location VUmc, Amsterdam, The Netherlands aff002;  School of Chemistry, The University of Sydney, Sydney, Australia aff003;  Department of Epidemiology and Biostatistics, Amsterdam UMC| location VUmc, Amsterdam, The Netherlands aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222844

Souhrn

Background

Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-[11C]PK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO PET for RA imaging, second generation TSPO tracers [11C]DPA-713 and [18F]DPA-714 have recently been evaluated pre-clinically showing better imaging characteristics.

Objective

A clinical proof of concept study to evaluate [11C]DPA-713 and [18F]DPA-714 to visualize arthritis in RA patients.

Methods

RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of [18F]DPA-714, [11C]DPA-713 and/or (R)-[11C]PK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison.

Results

Clinically active arthritis was present in 110 hand joints (2–17 pp). Arthritic joints were visualized with both [11C]DPA-713 and [18F]DPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for [11C]DPA-713 than for [18F]DPA-714, the latter being not significantly different from (R)-[11C]PK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-[11C]PK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for [11C]DPA-713.

Conclusions

[11C]DPA-713 and [18F]DPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for [11C]DPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.

Klíčová slova:

Arthritis – Blood – Macrophages – NSAIDs – Positron emission tomography – Rheumatoid arthritis – Skeletal joints


Zdroje

1. Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964–75. doi: 10.1136/ard.2009.126532 20444750; PubMed Central PMCID: PMC2935329.

2. Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997;350(9074):309–18. doi: 10.1016/S0140-6736(97)01300-7 9251634.

3. Landewe RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46(2):347–56. doi: 10.1002/art.10083 11840436.

4. Jones T. The role of positron emission tomography within the spectrum of medical imaging. Eur J Nucl Med. 1996;23(2):207–11. doi: 10.1007/bf01731847 8925858.

5. Haringman JJ, Gerlag DM, Zwinderman AH, Smeets TJ, Kraan MC, Baeten D, et al. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005;64(6):834–8. doi: 10.1136/ard.2004.029751 15576415; PubMed Central PMCID: PMC1755544.

6. Kraan MC, Versendaal H, Jonker M, Bresnihan B, Post WJ, t Hart BA, et al. Asymptomatic synovitis precedes clinically manifest arthritis. Arthritis Rheum. 1998;41(8):1481–8. doi: 10.1002/1529-0131(199808)41:8<1481::AID-ART19>3.0.CO;2-O 9704648.

7. Gent YY, Voskuyl AE, Kloet RW, van Schaardenburg D, Hoekstra OS, Dijkmans BA, et al. Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study. Arthritis Rheum. 2012;64(1):62–6. doi: 10.1002/art.30655 21898356.

8. van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, et al. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008;58(11):3350–5. doi: 10.1002/art.23955 18975347.

9. Gent YY, Ter Wee MM, Voskuyl AE, den Uyl D, Ahmadi N, Dowling C, et al. Subclinical synovitis detected by macrophage PET, but not MRI, is related to short-term flare of clinical disease activity in early RA patients: an exploratory study. Arthritis Res Ther. 2015;17:266. doi: 10.1186/s13075-015-0770-7 26403667; PubMed Central PMCID: PMC4582930.

10. Gent YY, Ahmadi N, Voskuyl AE, Hoetjes N, van Kuijk C, Britsemmer K, et al. Detection of subclinical synovitis with macrophage targeting and positron emission tomography in patients with rheumatoid arthritis without clinical arthritis. J Rheumatol. 2014;41(11):2145–52. doi: 10.3899/jrheum.140059 25274888.

11. James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, et al. DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med. 2008;49(5):814–22. doi: 10.2967/jnumed.107.046151 18413395.

12. Thominiaux C, Dolle F, James ML, Bramoulle Y, Boutin H, Besret L, et al. Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate. Appl Radiat Isot. 2006;64(5):570–3. doi: 10.1016/j.apradiso.2005.12.003 16427784.

13. Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A, et al. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009;50(3):468–76. doi: 10.2967/jnumed.108.058669 19223401.

14. Doorduin J, Klein HC, Dierckx RA, James M, Kassiou M, de Vries EF. [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis. Mol Imaging Biol. 2009;11(6):386–98. doi: 10.1007/s11307-009-0211-6 19330384; PubMed Central PMCID: PMC2763079.

15. Dupont AC, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Tronel C, Arlicot N. Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases. Int J Mol Sci. 2017;18(4). doi: 10.3390/ijms18040785 28387722; PubMed Central PMCID: PMC5412369.

16. Gent YY, Weijers K, Molthoff CF, Windhorst AD, Huisman MC, Kassiou M, et al. Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis. Arthritis Res Ther. 2014;16(2):R70. doi: 10.1186/ar4509 24625077; PubMed Central PMCID: PMC4060541.

17. Narayan N, Owen DR, Mandhair H, Smyth E, Carlucci F, Saleem A, et al. Translocator Protein as an Imaging Marker of Macrophage and Stromal Activation in Rheumatoid Arthritis Pannus. J Nucl Med. 2018;59(7):1125–32. Epub 2018/01/06. doi: 10.2967/jnumed.117.202200 29301931.

18. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580–8. doi: 10.1136/ard.2010.138461 20699241.

19. Boellaard R, Hoekstra O, Lammertsma A. Software tools for standardized analysis of FDG whole body studies in multi-center trials. J NUCL MED. 2008;49.

20. Krak NC, Boellaard R, Hoekstra OS, Twisk JW, Hoekstra CJ, Lammertsma AA. Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging. 2005;32(3):294–301. doi: 10.1007/s00259-004-1566-1 15791438.

21. Vanderhoek M, Perlman SB, Jeraj R. Impact of the definition of peak standardized uptake value on quantification of treatment response. J Nucl Med. 2012;53(1):4–11. doi: 10.2967/jnumed.111.093443 22213818; PubMed Central PMCID: PMC3308343.

22. Owen DR, Guo Q, Rabiner EA, Gunn RN. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clinical and Translational Imaging. 2015;3(6):417–22. doi: 10.1007/s40336-015-0141-z

23. Mizrahi R, Rusjan PM, Kennedy J, Pollock B, Mulsant B, Suridjan I, et al. Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA. J Cereb Blood Flow Metab. 2012;32(6):968–72. doi: 10.1038/jcbfm.2012.46 22472607; PubMed Central PMCID: PMC3367231.

24. Scarf AM, Kassiou M. The translocator protein. J Nucl Med. 2011;52(5):677–80. doi: 10.2967/jnumed.110.086629 21498529.

25. Bruijnen ST, Gent YY, Voskuyl AE, Hoekstra OS, van der Laken CJ. Present role of positron emission tomography in the diagnosis and monitoring of peripheral inflammatory arthritis: a systematic review. Arthritis Care Res (Hoboken). 2014;66(1):120–30. doi: 10.1002/acr.22184 24124027.


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden