{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T16:10:22Z","timestamp":1778947822790,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Turku University Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005633","name":"Syd\u00e4ntutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100005633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007634","name":"Ida Montinin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007634","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [18F]Flutemetamol in atherosclerotic plaques. The binding of [18F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II\/LDLR\u2212\/\u2212ApoB100\/100 mice and C57BL\/6N controls. Tracer biodistribution was studied in vivo with PET\/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [18F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II\/LDLR\u2212\/\u2212ApoB100\/100 mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET\/CT. In conclusion, [18F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.<\/jats:p>","DOI":"10.3390\/molecules24061072","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T12:12:25Z","timestamp":1552997545000},"page":"1072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-3693","authenticated-orcid":false,"given":"Sanna","family":"Hellberg","sequence":"first","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna M.U.","family":"Silvola","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-1584","authenticated-orcid":false,"given":"Heidi","family":"Liljenb\u00e4ck","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"},{"name":"Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Kiugel","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olli","family":"Eskola","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-045X","authenticated-orcid":false,"given":"Harri","family":"Hakovirta","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Turku University Hospital, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohvi","family":"H\u00f6rkk\u00f6","sequence":"additional","affiliation":[{"name":"Medical Research Center and Nordlab Oulu, University Hospital and Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronique","family":"Morisson-Iveson","sequence":"additional","affiliation":[{"name":"GE Healthcare Ltd., Chalfont St Giles HP8 4SP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Hirani","sequence":"additional","affiliation":[{"name":"GE Healthcare Ltd., Chalfont St Giles HP8 4SP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pekka","family":"Saukko","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-2708","authenticated-orcid":false,"given":"Seppo","family":"Yl\u00e4-Herttuala","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antti","family":"Saraste","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"},{"name":"Turku PET Centre, Turku University Hospital, FI-20520 Turku, Finland"},{"name":"Heart Center, Turku University Hospital, FI-20520 Turku, Finland"},{"name":"Department of Clinical Medicine, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-7977","authenticated-orcid":false,"given":"Anne","family":"Roivainen","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"},{"name":"Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2009.09.009","article-title":"Inflammation in Atherosclerosis. From Pathophysiology to Practice","volume":"54","author":"Libby","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/S0140-6736(04)15900-X","article-title":"Convergence of atherosclerosis and Alzheimer\u2019s disease: Inflammation, cholesterol, and misfolded proteins","volume":"363","author":"Casserly","year":"2004","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lathe, R., Sapronova, A., and Kotelevtsev, Y. (2014). Atherosclerosis and Alzheimer\u2014Diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr., 14.","DOI":"10.1186\/1471-2318-14-36"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15977","DOI":"10.1016\/S0021-9258(18)55493-4","article-title":"The amyloid precursor protein of Alzheimer\u2019s disease is released by human platelets","volume":"265","author":"Bush","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40097","DOI":"10.1074\/jbc.M110.144626","article-title":"Brain endothelial cells produce amyloid \u03b2 from amyloid precursor protein 770 and preferentially secrete the O-glycosylated form","volume":"285","author":"Kitazume","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1073\/pnas.89.13.6075","article-title":"Beta-amyloid precursor protein cleavage by a membrane-bound protease","volume":"89","author":"Sisodia","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40817","DOI":"10.1074\/jbc.M112.398578","article-title":"Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: A novel biomarker for acute coronary syndrome","volume":"287","author":"Kitazume","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jacc.2014.12.035","article-title":"Amyloid-Beta (1-40) and the Risk of Death from Cardiovascular Causes in Patients with Coronary Heart Disease","volume":"65","author":"Stamatelopoulos","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1161\/01.CIR.0000115516.54550.B1","article-title":"Serum Amyloid A as a Predictor of Coronary Artery Disease and Cardiovascular Outcome in Women: The National Heart; Lung; and Blood Institute-Sponsored Women\u2019s Ischemia Syndrome Evaluation (WISE)","volume":"109","author":"Johnson","year":"2004","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH753>3.0.CO;2-S","article-title":"Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta","volume":"193","author":"Mucchiano","year":"2001","journal-title":"J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1161\/01.RES.0000020017.84398.61","article-title":"Platelet phagocytosis and processing of \u03b2-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis","volume":"90","author":"Cooper","year":"2002","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.bbadis.2011.07.004","article-title":"Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets","volume":"1812","author":"Kokjohn","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.atherosclerosis.2009.10.040","article-title":"Increased atherosclerosis and vascular inflammation in APP transgenic mice with apolipoprotein E deficiency","volume":"210","author":"Tibolla","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.atherosclerosis.2011.01.032","article-title":"Attenuated atherogenesis in apolipoprotein E-deficient mice lacking amyloid precursor protein","volume":"216","author":"Guns","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11811","DOI":"10.1016\/S0021-9258(19)50272-1","article-title":"CD36 is a receptor for oxidized low density lipoprotein","volume":"268","author":"Endemann","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI14006","article-title":"CD36: A class B scavenger receptor involved in angiogenesis; atherosclerosis; inflammation; and lipid metabolism","volume":"108","author":"Febbraio","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9108","DOI":"10.1021\/bi050497v","article-title":"Oxidation of low-density lipoproteins induces amyloid-like structures that are recognized by macrophages","volume":"44","author":"Stewart","year":"2005","journal-title":"Biochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ana.20009","article-title":"Imaging Brain Amyloid in Alzheimer\u2019s Disease with Pittsburgh Compound-B","volume":"55","author":"Klunk","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S1474-4422(11)70123-5","article-title":"Clinical amyloid imaging in Alzheimer\u2019s disease","volume":"10","author":"Herholz","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00259-017-3651-2","article-title":"Feasibility of in vivo 18F-florbetaben PET\/MR imaging of human carotid amyloid-\u03b2","volume":"44","author":"Bucerius","year":"2017","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2967\/jnumed.111.102053","article-title":"In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET","volume":"54","author":"Antoni","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1007\/s00259-014-2787-6","article-title":"Imaging cardiac amyloidosis: A pilot study using 18F-florbetapir positron emission tomography","volume":"41","author":"Dorbala","year":"2014","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.2967\/jnumed.109.063305","article-title":"Phase 1 study of the Pittsburgh compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease","volume":"50","author":"Nelissen","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41810","DOI":"10.1074\/jbc.M303925200","article-title":"Glycation Induces Formation of Amyloid Cross-\u03b2 Structure in Albumin","volume":"278","author":"Bouma","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.107.154401","article-title":"Increased atherosclerotic lesion calcification in a novel mouse model combining insulin resistance; hyperglycemia; and hypercholesterolemia","volume":"101","author":"Heinonen","year":"2007","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1161\/01.ATV.20.3.689","article-title":"In vivo uptake of radiolabeled MDA2; an oxidation-specific monoclonal antibody; provides an accurate measure of atherosclerotic lesions rich in oxidized LDL and is highly sensitive to their regression","volume":"20","author":"Tsimikas","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.nucmedbio.2012.08.002","article-title":"Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques","volume":"40","author":"Nishigori","year":"2013","journal-title":"Nucl. Med. Biol."},{"key":"ref_28","first-page":"871","article-title":"Senile aortic amyloid. Evidence for two distinct forms of localized deposits","volume":"140","author":"Mucchiano","year":"1992","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10598","DOI":"10.1523\/JNEUROSCI.2990-05.2005","article-title":"Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer\u2019s disease brain but not in transgenic mouse brain","volume":"25","author":"Klunk","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fnins.2014.00327","article-title":"A review of \u03b2-amyloid neuroimaging in Alzheimer\u2019s disease","volume":"8","author":"Adlard","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1007\/s00259-012-2178-9","article-title":"Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer\u2019s disease","volume":"39","author":"Snellman","year":"2012","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1007\/s00259-009-1220-z","article-title":"68Ga-DOTA-RGD peptide: Biodistribution and binding into atherosclerotic plaques in mice","volume":"36","author":"Haukkala","year":"2009","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lehti, S., K\u00e4kel\u00e4, R., H\u00f6rkk\u00f6, S., Kummu, O., Helske-Suihko, S., Kupari, M., Werkkala, K., Kovanen, P.T., and \u00d6\u00f6rni, K. (2013). Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065810"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/6\/1072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:53Z","timestamp":1760186333000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/6\/1072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,19]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["molecules24061072"],"URL":"https:\/\/doi.org\/10.3390\/molecules24061072","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,19]]}}}