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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2014

Open Access 01-04-2014 | Research article

[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model

Authors: Géraldine Pottier, Nicholas Bernards, Frédéric Dollé, Raphael Boisgard

Published in: Arthritis Research & Therapy | Issue 2/2014

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Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Today, diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. The present study aims to investigate the potential of [18F]DPA-714 to monitor in vivo inflammatory processes at a preclinical stage via positron emission tomography (PET).

Methods

RA was induced in Dark Agouti rats by subcutaneous injection of inactivated Mycobacterium tuberculosis. Development of arthritis clinical signs was investigated daily and the severity of the disease evaluated. Animals were imaged at the peak of inflammation using [18F]DPA-714 and a small-animal PET-CT tomograph.

Results

The first clinical signs appeared at 10 days post-injection, with a peak of inflammation at 20 days. At this time, PET-analyses showed a clear uptake of [18F]DPA-714 in swollen ankles, with mean values of 0.52 ± 0.18% injected dose (ID/cc) for treated (n = 11) and 0.19 ± 0.09 for non-treated (n = 6) rats. A good correlation between [18F]DPA-714’s uptake and swelling was also found. Immunohistochemistry showed an enhanced TSPO expression in hind paws, mainly co-localized with the macrophages specific antigen CD68 expressing cells.

Conclusion

These preliminary results demonstrate that the TSPO 18kDa specific radioligand [18F]DPA-714 is adapted for the study and follow-up of inflammation linked to RA in our experimental model, suggesting also a strong potential for clinical imaging of peripheral inflammation.
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Literature
1.
Scott DL, Wolfe F, Huizinga TW: Rheumatoid arthritis. Lancet. 2010, 376: 1094-1108. 10.1016/S0140-6736(10)60826-4.CrossRefPubMed
2.
Liao KP, Alfredsson L, Karlson EW: Environmental influences on risk for rheumatoid arthritis. Curr Opin Rheumatol. 2009, 21: 279-283. 10.1097/BOR.0b013e32832a2e16.PubMedCentralCrossRefPubMed
3.
Banal F, Dougados M, Combescure C, Gossec L: Sensitivity and specificity of the American College of Rheumatology 1987 criteria for the diagnosis of rheumatoid arthritis according to disease duration: a systematic literature review and meta-analysis. Ann Rheum Dis. 2009, 68: 1184-1191. 10.1136/ard.2008.093187.CrossRefPubMed
4.
Wakefield RJ, Gibbon WW, Conaghan PG, O’Connor P, McGonagle D, Pease C, Green MJ, Veale DJ, Isaacs JD, Emery P: The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum. 2000, 43: 2762-2770. 10.1002/1529-0131(200012)43:12<2762::AID-ANR16>3.0.CO;2-#.CrossRefPubMed
5.
Perić P, Laktasić-Zerjavić N: The value of sonography and power Doppler in the detection of early arthritis. Reumatizam. 2011, 58: 94-104.PubMed
6.
van de Stadt LA, Bos WH, Meursinge Reynders M, Wieringa H, Turkstra F, van der Laken CJ, van Schaardenburg D: The value of ultrasonography in predicting arthritis in auto-antibody positive arthralgia patients: a prospective cohort study. Arthritis Res Ther. 2010, 12: R98-10.1186/ar3028.PubMedCentralCrossRefPubMed
7.
Gent YY, Voskuyl AE, Kloet RW, van Schaardenburg D, Hoekstra OS, Dijkmans BA, Lammertsma AA, van der Laken CJ: Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study. Arthritis Rheum. 2012, 64: 62-66. 10.1002/art.30655.CrossRefPubMed
8.
Okamura K, Yonemoto Y, Arisaka Y, Takeuchi K, Kobayashi T, Oriuchi N, Tsushima Y, Takagishi K: The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT. Rheumatology (Oxford). 2012, 51: 1484-1491. 10.1093/rheumatology/kes064.CrossRef
9.
Kubota K, Ito K, Morooka M, Minamimoto R, Miyata Y, Yamashita H, Takahashi Y, Mimori A: FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT. Ann N Y Acad Sci. 2011, 1228: 29-38. 10.1111/j.1749-6632.2011.06031.x.CrossRefPubMed
10.
van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, Boellaard R, Dijkmans BAC, Lammertsma AA, Voskuy AE: Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008, 58: 3350-3355. 10.1002/art.23955.CrossRefPubMed
11.
Polisson RP, Schoenberg OI, Fischman A, Rubin R, Simon LS, Rosenthal D, Palmer WE: Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 819-825. 10.1002/art.1780380616.CrossRefPubMed
12.
Irmler IM, Opfermann T, Gebhardt P, Gajda M, Brauer R, Saluz HP, Kamradt T: In vivo molecular imaging of experimental joint inflammation by combined 18F-FDG positron emission tomography and computed tomography. Arthritis Res Ther. 2010, 12: R203-10.1186/ar3176.PubMedCentralCrossRefPubMed
13.
Kraan MC, Versendaal H, Jonker M, Bresnihan B, Post WJ, Hart BA, Breedveld FC, Tak PP: Asymptomatic synovitis precedes clinically manifest arthritis. Arthritis Rheum. 1998, 41: 1481-1488. 10.1002/1529-0131(199808)41:8<1481::AID-ART19>3.0.CO;2-O.CrossRefPubMed
14.
Gent YY, Weijers K, Molthoff CF, Windhorst AD, Huisman MC, Smith DE, Kularatne SA, Jansen G, Low PS, Lammertsma AA, van der Laken J: Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis. Arthritis Res Ther. 2013, 15: R37-10.1186/ar4191.PubMedCentralCrossRefPubMed
15.
Casellas P, Galiegue S, Basile S: Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 2002, 40: 475-486. 10.1016/S0197-0186(01)00118-8.CrossRefPubMed
16.
Tang D, Hight MR, McKinley ET, Fu A, Buck JR, Smith RA, Tantawy MN, Peterson TE, Colvin DC, Ansari MS, Nickels M, Manning HC: Quantitative preclinical imaging of TSPO expression in glioma using N, N-diethyl-2-(2-(4-(2–18F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide. J Nucl Med. 2012, 53: 287-294. 10.2967/jnumed.111.095653.PubMedCentralCrossRefPubMed
17.
Martín A, Boisgard R, Kassiou M, Dollé F, Tavitian B: Reduced PBR/TSPO expression after minocycline treatment in a rat model of focal cerebral ischemia: a PET study using [18F]DPA-714. Mol Imaging Biol. 2011, 13: 10-15. 10.1007/s11307-010-0324-y.CrossRefPubMed
18.
Hatori A, Yui J, Yamasaki T, Xie L, Kumata K, Fujinaga M, Yoshida Y, Ogawa M, Nengaki N, Kawamura K, Fukumura T, Zhang M-R: PET imaging of lung inflammation with [18F]FEDAC, a radioligand for translocator protein (18kDa). PLoS One. 2012, 7: e45065-10.1371/journal.pone.0045065.PubMedCentralCrossRefPubMed
19.
Xie L, Yui J, Hatori A, Yamasaki T, Kumata K, Wakizaka H, Yoshida Y, Fujinaga M, Kawamura K, Zhang M-R: Translocator protein (18kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease. J Hepatol. 2012, 57: 1076-1082. 10.1016/j.jhep.2012.07.002.CrossRefPubMed
20.
Chauveau F, Boutin H, Van Camp N, Dollé F, Tavitian B: Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008, 35: 2304-2319. 10.1007/s00259-008-0908-9.CrossRefPubMed
21.
Dollé F, Luus C, Reynolds A, Kassiou M: Radiolabelled molecules for imaging the translocator protein (18kDa) using positron emission tomography. Curr Med Chem. 2009, 16: 2899-2923. 10.2174/092986709788803150.CrossRefPubMed
22.
Roeda D, Kuhnast B, Damont A, Dollé F: Synthesis of fluorine-18-labelled TSPO ligands for imaging neuroinflammation with positron emission tomography. J Fluor Chem. 2012, 134: 107-114.CrossRef
23.
Damont A, Roeda D, Dollé F: The potential of carbon-11 and fluorine-18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa. J Labelled Comp Radiopharm. 2013, 56: 96-104. 10.1002/jlcr.2992.CrossRefPubMed
24.
Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R: Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18kDa translocator protein radioligand [18F]DPA-714. J Neurosci. 2012, 32: 5728-5736. 10.1523/JNEUROSCI.2900-11.2012.CrossRefPubMed
25.
Winkeler A, Boisgard R, Martin A, Tavitian B: Radioisotopic imaging of neuroinflammation. J Nucl Med. 2010, 51: 1-4. 10.2967/jnumed.109.065680.CrossRefPubMed
26.
Chauveau F, Van Camp N, Dollé F, Kuhnast B, Hinnen F, Damont A, Boutin H, James M, Kassiou M, Tavitian B: 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: 468-476. 10.2967/jnumed.108.058669.CrossRefPubMed
27.
Zheng J, Boisgard R, Siquier-Pernet K, Decaudin D, Dollé F, Tavitian B: Differential expression of the 18kDa translocator protein (TSPO) by neoplastic and inflammatory cells in mouse tumors of breast cancer. Mol Pharm. 2011, 8: 823-832. 10.1021/mp100433c.CrossRefPubMed
28.
Winkeler A, Boisgard R, Awde AR, Dubois A, Thézé B, Zheng J, Ciobanu L, Dollé F, Viel T, Jacobs AH, Tavitian B: The translocator protein ligand [18F]DPA-714 images glioma and activated microglia in vivo. Eur J Nucl Med Mol Imaging. 2012, 39: 811-823. 10.1007/s00259-011-2041-4.PubMedCentralCrossRefPubMed
29.
Kropholler M, Boellaard R, Elzinga E, van der Laken C, Maruyama K, Kloet R, Voskuyl A, Dijkmans B, Lammertsma A: Quantification of ( R)-[11C]PK11195 binding in rheumatoid arthritis. Eur J Nucl Med Mol Imaging. 2009, 36: 624-631. 10.1007/s00259-008-0987-7.CrossRefPubMed
30.
James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, Dolle F, Costa B, Selleri S, Guilloteau D, Kassiou M: DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med. 2008, 49: 814-822. 10.2967/jnumed.107.046151.CrossRefPubMed
31.
Damont A, Hinnen F, Kuhnast B, Schöllhorn-Peyronneau M-A, James M, Luus C, Tavitian B, Kassiou M, Dollé F: Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18kDa) with PET. J Labelled Comp Radiopharm. 2008, 51: 286-292. 10.1002/jlcr.1523.CrossRef
32.
Kuhnast B, Damont A, Hinnen F, Catarina T, Demphel S, Le Helleix S, Coulon C, Goutal S, Gervais P, Dollé F: [18F]DPA-714, [18F]PBR111 and [18F]FEDAA1106-selective radioligands for imaging TSPO 18kDa with PET: automated radiosynthesis on a TRACERLAb FX-FN synthesizer and quality controls. Appl Radiat Isot. 2012, 70: 489-497. 10.1016/j.apradiso.2011.10.015.CrossRefPubMed
33.
Cointepas Y, Mangin J-F, Garnero L, Poline J-B, Benali H: BrainVISA: Software platform for visualization and analysis of multi-modality brain data. Neuroimage. 2001, 13: S98-10.1016/S1053-8119(01)91441-7.CrossRef
34.
Colebatch AN, Edwards CJ, Østergaard M, van der Heijde D, Balint PV, D’Agostino M-A, Forslind K, Grassi W, Haavardsholm EA, Haugeberg G, Jurik A-G, Landewé RB, Naredo E, O’Connor PJ, Ostendorf B, Potočki K, Schmidt WA, Smolen JS, Sokolovic S, Watt I, Conaghan PG: EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013, 72: 804-814. 10.1136/annrheumdis-2012-203158.CrossRefPubMed
Metadata
Title
[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model
Authors
Géraldine Pottier
Nicholas Bernards
Frédéric Dollé
Raphael Boisgard
Publication date
01-04-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4508

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