[en] OBJECTIVE: This work reports on musculoskeletal uptake of (18)F-FPRGD2, targeting the integrin alphavbeta3, in patients who had undergone (18)F-FPRGD2 positron emission tomography combined with computed tomography (PET/CT) for oncologic purposes. METHODS: Whole-body (18)F-FPRGD2 PET/CT images of 62 cancer patients were retrospectively reviewed to detect foci of musculoskeletal (18)F-FPRGD2 uptake. For 37 patients, a FDG PET/CT performed in clinical settings was available. In each joint with an abnormal uptake, the maximum standardized uptake value (SUVmax) was estimated. RESULTS: A total of 260 musculoskeletal foci of (18)F-FPRGD2 uptake were detected. Most common sites of uptake were joints and discs (n = 160; 61.5 %), entheses (osteotendinous and osteoligamentous junctions; n = 55; 21.2 %) and recent fractures (n = 18; 6.9 %). In addition, 27 (10.4 %) miscellaneous foci were detected. Out of the 146 lesions for which a FDG PET was available, 63 % showed both (18)F-FPRGD2 and FDG uptake, 33.6 % did not show FDG avidity and 3.4 % showed only FDG uptake. The uptake intensity of the 92 lesions positive with (18)F-FPRGD2 and FDG was similar with both radiopharmaceuticals, but the target-to-background (blood pool or muscle) ratios were significantly higher with (18)F-FPRGD2 than with FDG (p < 0.0001). CONCLUSION: The (18)F-FPRGD2 uptake in joints, spine degenerative diseases and tendons was highly prevalent in our population. Up to one-third of (18)F-FPRGD2 foci showed no FDG uptake suggesting that (18)F-FPRGD2 signal may not be related to inflammatory angiogenesis only.
Disciplines :
Rheumatology Radiology, nuclear medicine & imaging
Author, co-author :
WITHOFS, Nadia ; Centre Hospitalier Universitaire de Liège - CHU > Service médical de médecine nucléaire et imagerie onco
CHARLIER, Edith ; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Simoni, Paolo
Alvarez-Miezentseva, Victoria
Mievis, Frédéric ; Université de Liège > Centre de recherches du cyclotron
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Bibliography
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–30.
Moyer RF, Ratneswaran A, Beier F, Birmingham TB. Osteoarthritis year in review 2014: mechanics–basic and clinical studies in osteoarthritis. Osteoarthritis Cartilage. 2014;22(12):1989–2002.
Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, et al. Osteoarthritis. Lancet. 2015 (pii: S0140-6736(14)60802-3).
Jungmann PM, Kraus MS, Alizai H, Nardo L, Baum T, Nevitt MC, et al. Association of metabolic risk factors with cartilage degradation assessed by T2 relaxation time at the knee: data from the osteoarthritis initiative. Arthritis Care Res. 2013;65(12):1942–50.
Mobasheri A. Osteoarthritis year 2012 in review: biomarkers. Osteoarthritis Cartilage. 2012;20(12):1451–64.
de Seny D, Sharif M, Fillet M, Cobraiville G, Meuwis MA, Maree R, et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann Rheum Dis. 2011;70(6):1144–52.
Henrotin Y, Gharbi M, Mazzucchelli G, Dubuc JE, De Pauw E, Deberg M. Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis. Arthritis Rheum. 2012;64(7):2260–7.
Beckers C, Jeukens X, Ribbens C, Andre B, Marcelis S, Leclercq P, et al. 18F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging. 2006;33(3):275–80.
Wu Z, Li ZB, Cai W, He L, Chin FT, Li F, et al. 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of αvβ3 integrin expression. Eur J Nucl Med Mol Imaging. 2007;34(11):1823–31.
Gaertner FC, Kessler H, Wester HJ, Schwaiger M, Beer AJ. Radiolabelled RGD peptides for imaging and therapy. Eur J Nucl Med Mol Imaging. 2012;39(Suppl 1):S126–38.
Vogetseder A, Thies S, Ingold B, Roth P, Weller M, Schraml P, et al. αv-Integrin isoform expression in primary human tumors and brain metastases. Int J Cancer. 2013;133(10):2362–71.
Rinaldi N, Weis D, Brado B, Schwarz-Eywill M, Lukoschek M, Pezzutto A, et al. Differential expression and functional behaviour of the αvβ3 integrin subunits in cytokine stimulated fibroblast-like cells derived from synovial tissue of rheumatoid arthritis and osteoarthritis in vitro. Ann Rheum Dis. 1997;56(12):729–36.
Nam EJ, Sa KH, You DW, Cho JH, Seo JS, Han SW, et al. Up-regulated transforming growth factor β-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through αvβ3 integrin: Regulation by cytokines. Arthritis Rheum. 2006;54(9):2734–44.
Hou CH, Tang CH, Hsu CJ, Hou SM, Liu JF. CCN4 induces IL-6 production through αvβ5 receptor, PI3 K, Akt, and NF-κB singling pathway in human synovial fibroblasts. Arthritis Res Ther. 2013;15(1):R19.
Woods VL Jr, Schreck PJ, Gesink DS, Pacheco HO, Amiel D, Akeson WH, et al. Integrin expression by human articular chondrocytes. Arthritis Rheum. 1994;37(4):537–44.
Ostergaard K, Salter DM, Petersen J, Bendtzen K, Hvolris J, Andersen CB. Expression of α and β subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads. Ann Rheum Dis. 1998;57(5):303–8.
Fukui N, Ikeda Y, Tanaka N, Wake M, Yamaguchi T, Mitomi H, et al. αvβ5 integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes. Arthritis Rheum. 2011;63(7):1938–49.
Loeser RF. Integrin-mediated attachment of articular chondrocytes to extracellular matrix proteins. Arthritis Rheum. 1993;36(8):1103–10.
Salter DM, Hughes DE, Simpson R, Gardner DL. Integrin expression by human articular chondrocytes. Br J Rheumatol. 1992;31(4):231–4.
Attur MG, Dave MN, Clancy RM, Patel IR, Abramson SB, Amin AR. Functional genomic analysis in arthritis-affected cartilage: yin-yang regulation of inflammatory mediators by α5β1 and αvβ3 integrins. J Immunol. 2000;164(5):2684–91.
Kurtis MS, Schmidt TA, Bugbee WD, Loeser RF, Sah RL. Integrin-mediated adhesion of human articular chondrocytes to cartilage. Arthritis Rheum. 2003;48(1):110–8.
Nakamura I, le Duong T, Rodan SB, Rodan GA. Involvement of αvβ3 integrins in osteoclast function. J Bone Miner Metab. 2007;25(6):337–44.
Thi MM, Suadicani SO, Schaffler MB, Weinbaum S, Spray DC. Mechanosensory responses of osteocytes to physiological forces occur along processes and not cell body and require αvβ3 integrin. Proc Natl Acad Sci USA. 2013.
Nettles DL, Richardson WJ, Setton LA. Integrin expression in cells of the intervertebral disc. J Anat. 2004;204(6):515–20.
Gilbert HT, Nagra NS, Freemont AJ, Millward-Sadler SJ, Hoyland JA. Integrin-dependent mechanotransduction in mechanically stimulated human annulus fibrosus cells: evidence for an alternative mechanotransduction pathway operating with degeneration. PLoS ONE. 2013;8(9):e72994.
Tian J, Zhang FJ, Lei GH. Role of integrins and their ligands in osteoarthritic cartilage. Rheumatol Int. 2015;35(5):787–98.
Loeser RF. Integrins and chondrocyte-matrix interactions in articular cartilage. Matrix Biol. 2014;39:11–6.
Zheleznyak A, Wadas TJ, Sherman CD, Wilson JM, Kostenuik PJ, Weilbaecher KN, et al. Integrin αvβ3 as a PET imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation. Mol Imaging Biol. 2012;14(4):500–8.
Sprague JE, Kitaura H, Zou W, Ye Y, Achilefu S, Weilbaecher KN, et al. Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. J Nucl Med. 2007;48(2):311–8.
Zhu Z, Yin Y, Zheng K, Li F, Chen X, Zhang F, et al. Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using 68Ga-PRGD2 PET/CT: a prospective proof-of-concept cohort study. Ann Rheum Dis. 2014;73(6):1269–72.
Withofs N, Signolle N, Somja J, Lovinfosse P, Nzaramba EM, Mievis F, et al. 18F-FPRGD2 PET/CT imaging of integrin αvβ3 in renal carcinomas: correlation with histopathology. J Nucl Med. 2015;56(3):361–4.
Thonon D, Goblet D, Goukens E, Kaisin G, Paris J, Aerts J, et al. Fully automated preparation and conjugation of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) with RGD peptide using a GE FASTlab synthesizer. Mol Imaging Biol. 2011;13(6):1088–95.
Weishaupt D, Zanetti M, Boos N, Hodler J. MR imaging and CT in osteoarthritis of the lumbar facet joints. Skeletal Radiol. 1999;28(4):215–9.
Kettler A, Wilke HJ. Review of existing grading systems for cervical or lumbar disc and facet joint degeneration. Eur Spine J. 2006;15(6):705–18.
Videman T, Battie MC, Ripatti S, Gill K, Manninen H, Kaprio J. Determinants of the progression in lumbar degeneration: a 5-year follow-up study of adult male monozygotic twins. Spine (Phila Pa 1976). 2006;31(6):671–8.
Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.
Gkretsi V, Papanikolaou V, Dubos S, Papathanasiou I, Giotopoulou N, Valiakou V, et al. Migfilin’s elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation. Biochem Biophys Res Commun. 2013;430(2):494–9.
van der Kraan PM, van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthritis Cartilage. 2012;20(3):223–32.
Bertrand J, Cromme C, Umlauf D, Frank S, Pap T. Molecular mechanisms of cartilage remodelling in osteoarthritis. Int J Biochem Cell Biol. 2010;42(10):1594–601.
Blaney Davidson EN, Remst DF, Vitters EL, van Beuningen HM, Blom AB, Goumans MJ, et al. Increase in ALK1/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and mice. J Immunol. 2009;182(12):7937–45.
Finnson KW, Parker WL, Chi Y, Hoemann CD, Goldring MB, Antoniou J, et al. Endoglin differentially regulates TGF-β-induced Smad2/3 and Smad1/5 signalling and its expression correlates with extracellular matrix production and cellular differentiation state in human chondrocytes. Osteoarthritis Cartilage. 2010;18(11):1518–27.
Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int. 2013;2013:284873.
Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51(2):204–11.
Lotz M. Osteoarthritis year 2011 in review: biology. Osteoarthritis Cartilage. 2012;20(3):192–6.
Pesesse L, Sanchez C, Delcour JP, et al. Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis. Osteoarthritis Cartilage. 2013;21(12):1913–23.
Mena E, Owenius R, Turkbey B, Sherry R, Bratslavsky G, Macholl S, et al. [18F]fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins. Eur J Nucl Med Mol Imaging. 2014;41(10):1879–88.
Beer AJ, Lorenzen S, Metz S, Herrmann K, Watzlowik P, Wester HJ, et al. Comparison of integrin αvβ3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG. J Nucl Med. 2008;49(1):22–9.
Silman AJ, Hochberg MC. Osteoarthtritis. In: Siman AJ, Me H (ed) Epidemiology of the rheumatic diseases. Oxford Medical Publishing ed. 1993.
Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 2013;39(1):1–19.
Suri P, Hunter DJ, Rainville J, Guermazi A, Katz JN. Quantitative assessment of abdominal aortic calcification and associations with lumbar intervertebral disc height loss: the Framingham Study. Spine J. 2012;12(4):315–23.
Millar NL, Hueber AJ, Reilly JH, Xu Y, Fazzi UG, Murrell GA, et al. Inflammation is present in early human tendinopathy. Am J Sports Med. 2010;38(10):2085–91.
Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med. 2008;49(6):879–86.
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