Abstract
Objective
In this study, the feasibility and kinetic characteristics of the 68Ga-NOTA-RGD, a recently developed RGD peptide agent, were investigated for atherosclerosis imaging in comparison with 18FDG.
Methods
ApoE−/− mice were fed a high-fat diet for more than 20 weeks. To evaluate the feasibility, tissue uptakes of 68Ga-NOTA-RGD and 18FDG in the major organs were measured and compared between ApoE−/− and control mice. Animal PET imaging was also performed and relative uptake values in the thoracic aorta were compared between ApoE−/− and control mice. In humans, the kinetic characteristics and feasibility of 68Ga-NOTA-RGD PET were assessed in 4 patients with known coronary artery disease.
Results
In the tissue uptake study, the thoracic aorta showed higher uptake in ApoE−/− than in control mice with both 68Ga-NOTA-RGD and 18FDG (P < 0.001). On PET scans, the relative uptake values of the thoracic aorta were significantly higher in ApoE−/− with both 68Ga-NOTA-RGD (P = 0.024) and 18FDG (P = 0.038). In human PET, the appropriateness of reversible binding model and Logan plotting was clearly demonstrated. The aorta-to-jugular ratios were measured up to 1.25 and showed a tendency to correlate with the serum high-sensitivity C-reactive protein level (r = 0.899, P = 0.102).
Conclusions
68Ga-NOTA-RGD has potential as an in vivo atherosclerosis imaging agent. However, the lower imaging contrast and sensitivity of 68Ga-NOTA-RGD PET compared with 18FDG PET may be a limitation for clinical application.
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References
Hackett D, Davies G, Maseri A. Pre-existing coronary stenoses in patients with first myocardial infarction are not necessarily severe. Eur Heart J. 1988;9:1317–23.
Murabito JM, Evans JC, Larson MG, Levy D. Prognosis after the onset of coronary heart disease. An investigation of differences in outcome between the sexes according to initial coronary disease presentation. Circulation. 1993;88:2548–55.
Sanz J, Fayad ZA. Imaging of atherosclerotic cardiovascular disease. Nature. 2008;451:953–7.
Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, et al. Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med. 2006;47:1845–50.
Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol. 2006;48:1825–31.
Arauz A, Hoyos L, Zenteno M, Mendoza R, Alexanderson E. Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography. Pilot study. Clin Neurol Neurosurg. 2007;109:409–12.
Tahara N, Kai H, Yamagishi S, Mizoguchi M, Nakaura H, Ishibashi M, et al. Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol. 2007;49:1533–9.
Potter K, Lenzo N, Eikelboom JW, Arnolda LF, Beer C, Hankey GJ. Effect of long-term homocysteine reduction with B vitamins on arterial wall inflammation assessed by fluorodeoxyglucose positron emission tomography: a randomised double-blind, placebo-controlled trial. Cerebrovasc Dis. 2009;27:259–65.
Burtea C, Laurent S, Murariu O, Rattat D, Toubeau G, Verbruggen A, et al. Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA. Cardiovasc Res. 2008;78:148–57.
Waldeck J, Hager F, Holtke C, Lanckohr C, von Wallbrunn A, Torsello G, et al. Fluorescence reflectance imaging of macrophage-rich atherosclerotic plaques using an alphavbeta3 integrin-targeted fluorochrome. J Nucl Med. 2008;49:1845–51.
Laitinen I, Saraste A, Weidl E, Poethko T, Weber AW, Nekolla SG, et al. Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice. Circ Cardiovasc Imaging. 2009;2:331–8.
Jeong JM, Hong MK, Chang YS, Lee YS, Kim YJ, Cheon GJ, et al. Preparation of a promising angiogenesis PET imaging agent: 68 Ga-labeled c(RGDyK)-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid and feasibility studies in mice. J Nucl Med. 2008;49:830–6.
Zhang X, **ong Z, Wu Y, Cai W, Tseng JR, Gambhir SS, et al. Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2. J Nucl Med. 2006;47:113–21.
Patsenker E, Popov Y, Stickel F, Schneider V, Ledermann M, Sagesser H, et al. Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis. Hepatology. 2009;50:1501–11.
Tahara N, Imaizumi T, Virmani R, Narula J. Clinical feasibility of molecular imaging of plaque inflammation in atherosclerosis. J Nucl Med. 2009;50:331–4.
Aziz K, Berger K, Claycombe K, Huang R, Patel R, Abela GS. Noninvasive detection and localization of vulnerable plaque and arterial thrombosis with computed tomography angiography/positron emission tomography. Circulation. 2008;117:2061–70.
Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–24.
Graebe M, Pedersen SF, Borgwardt L, Hojgaard L, Sillesen H, Kjaer A. Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). Eur J Vasc Endovasc Surg. 2009;37:714–21.
Wu YW, Kao HL, Chen MF, Lee BC, Tseng WY, Jeng JS, et al. Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1. J Nucl Med. 2007;48:227–33.
Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med. 2009;50:1611–20.
Jaffer FA, Libby P, Weissleder R. Molecular imaging of cardiovascular disease. Circulation. 2007;116:1052–61.
Moulton KS, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E, et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA. 2003;100:4736–41.
Higuchi T, Bengel FM, Seidl S, Watzlowik P, Kessler H, Hegenloh R, et al. Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography. Cardiovasc Res. 2008;78:395–403.
Haukkala J, Laitinen I, Luoto P, Iveson P, Wilson I, Karlsen H, et al. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice. Eur J Nucl Med Mol Imaging. 2009;36:2058–67.
Yang SJ, Kim S, Choi HY, Kim TN, Yoo HJ, Seo JA, et al. High-sensitivity C-reactive protein in the low- and intermediate-Framingham risk score groups: analysis with (18)F-fluorodeoxyglucose positron emission tomography. Int J Cardiol. 2013;163:277–81.
Acknowledgments
This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A090633).
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Paeng, J.C., Lee, YS., Lee, J.S. et al. Feasibility and kinetic characteristics of 68Ga-NOTA-RGD PET for in vivo atherosclerosis imaging. Ann Nucl Med 27, 847–854 (2013). https://doi.org/10.1007/s12149-013-0757-x
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DOI: https://doi.org/10.1007/s12149-013-0757-x