{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:40:52Z","timestamp":1790840452822,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/16\/10\/32375"],"award-info":[{"award-number":["RG\/16\/10\/32375"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/17\/51\/33096"],"award-info":[{"award-number":["FS\/17\/51\/33096"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/16\/10\/32375"],"award-info":[{"award-number":["RG\/16\/10\/32375"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CH\/09\/002"],"award-info":[{"award-number":["CH\/09\/002"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RE\/18\/5\/34216"],"award-info":[{"award-number":["RE\/18\/5\/34216"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/16\/10\/32375"],"award-info":[{"award-number":["RG\/16\/10\/32375"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust Senior Investigator Award","award":["WT103782AIA"],"award-info":[{"award-number":["WT103782AIA"]}]},{"name":"Sir Jules Thorn Biomedical Research Award 2015","award":["15\/JTA"],"award-info":[{"award-number":["15\/JTA"]}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/14\/78\/31020"],"award-info":[{"award-number":["FS\/14\/78\/31020"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Service Research Scotland"},{"DOI":"10.13039\/100003186","name":"NRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003186","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Service Lothian Health Board"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Cardiovascular thrombosis is responsible a quarter of deaths annually worldwide. Current imaging methods for cardiovascular thrombosis focus on anatomical identification of thrombus but cannot determine thrombus age or activity. Molecular imaging techniques hold promise for identification and quantification of thrombosis in vivo. Our objective was to assess a novel optical and positron-emitting probe targeting Factor XIIIa (ENC2015) as biomarker of active thrombus formation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Optical and positron-emitting ENC2015 probes were assessed ex vivo using blood drawn from human volunteers and passed through perfusion chambers containing denuded porcine aorta as a model of arterial injury. Specificity of ENC2015 was established with co-infusion of a factor XIIIa inhibitor. In vivo18F-ENC2015 biodistribution, kinetics, radiometabolism, and thrombus binding were characterized in rats. Both Cy5 and fluorine-18 labelled ENC2015 rapidly and specifically bound to thrombi. Thrombus uptake was inhibited by a factor XIIIa inhibitor. 18F-ENC2015 remained unmetabolized over 8\u2009h when incubated in ex vivo human blood. In vivo, 42% of parent radiotracer remained in blood 60\u2009min post-administration. Biodistribution studies demonstrated rapid clearance from tissues with elimination via the urinary system. In vivo,18F-ENC2015 uptake was markedly increased in the thrombosed carotid artery compared to the contralateral patent artery (mean standard uptake value ratio of 2.40 vs. 0.74, P\u2009&amp;lt;\u20090.0001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion\u2003<\/jats:title>\n                  <jats:p>ENC2015 rapidly and selectively binds to acute thrombus in both an ex vivo human translational model and an in vivo rodent model of arterial thrombosis. This probe holds promise for the non-invasive identification of thrombus formation in cardiovascular disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjci\/jez207","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T19:12:28Z","timestamp":1565205148000},"page":"673-682","source":"Crossref","is-referenced-by-count":23,"title":["Non-invasive in vivo imaging of acute thrombosis: development of a novel factor XIIIa radiotracer"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-9655","authenticated-orcid":false,"given":"Jack P M","family":"Andrews","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Portal","sequence":"first","affiliation":[{"name":"Edinburgh Molecular Imaging Ltd., 9 Little France Road, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tashfeen","family":"Walton","sequence":"first","affiliation":[{"name":"Edinburgh Imaging facility QMRI, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G","family":"Macaskill","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W F","family":"Hadoke","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Alcaide Corral","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Lucatelli","sequence":"first","affiliation":[{"name":"Edinburgh Imaging facility QMRI, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Wilson","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Wilson","sequence":"first","affiliation":[{"name":"ImaginAb, Inc. U.S. 43 Hindry Avenue, Suite D, Inglewood, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"MacNaught","sequence":"first","affiliation":[{"name":"Edinburgh Imaging facility QMRI, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R","family":"Dweck","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Newby","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana A S","family":"Tavares","sequence":"first","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,13]]},"reference":[{"key":"2020052004581482800_jez207-B1","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.115.306841","article-title":"Global burden of thrombosis: epidemiologic aspects","volume":"118","author":"Wendelboe","year":"2016","journal-title":"Circ Res"},{"key":"2020052004581482800_jez207-B2","doi-asserted-by":"crossref","first-page":"928","DOI":"10.2214\/AJR.08.2166","article-title":"CT and MRI in diseases of the aorta","volume":"193","author":"Litmanovich","year":"2009","journal-title":"AJR Am J Roentgenol"},{"key":"2020052004581482800_jez207-B3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1161\/CIRCULATIONAHA.105.593418","article-title":"Aortic atherosclerotic disease and stroke","volume":"114","author":"Kronzon","year":"2006","journal-title":"Circulation"},{"key":"2020052004581482800_jez207-B4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/000331979504600109","article-title":"Doppler ultrasound in the diagnosis of venous thrombosis","volume":"46","author":"Markel","year":"1995","journal-title":"Angiology"},{"key":"2020052004581482800_jez207-B5","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrcardio.2009.201","article-title":"PET and SPECT in cardiovascular molecular imaging","volume":"7","author":"Dobrucki","year":"2010","journal-title":"Nat Rev Cardiol"},{"key":"2020052004581482800_jez207-B6","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1161\/CIRCIMAGING.113.001806","article-title":"In vivo molecular imaging of thrombosis and thrombolysis using a fibrin-binding positron emission tomographic probe","volume":"7","author":"Ay","year":"2014","journal-title":"Circ Cardiovasc Imaging"},{"key":"2020052004581482800_jez207-B7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.2967\/jnumed.118.212084","article-title":"Glycoprotein IIb\/IIIa receptor imaging with18F-GP1 PET for acute venous thromboembolism: an open-label, nonrandomized, phase 1 study","volume":"60","author":"Kim","year":"2019","journal-title":"J Nucl Med"},{"key":"2020052004581482800_jez207-B8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1124\/dmd.105.006239","article-title":"Nc100668, a new tracer for imaging of venous thromboembolism: disposition and metabolism in rats","volume":"34","author":"Skotland","year":"2005","journal-title":"Drug Metab Dispos"},{"key":"2020052004581482800_jez207-B9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jchromb.2005.09.031","article-title":"Quantification of NC100668, a new tracer for imaging of venous thromboembolism, in human plasma using reversed-phase liquid chromatography coupled with electrospray ionization ion-trap mass spectrometry","volume":"829","author":"Toft","year":"2005","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2020052004581482800_jez207-B10","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1007\/s00259-006-0091-9","article-title":"99m)Tc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro","volume":"33","author":"Edwards","year":"2006","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2020052004581482800_jez207-B11","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1124\/dmd.106.009696","article-title":"The in vivo and in vitro metabolic profile of 99mTc-NC100668, a new tracer for imaging venous thromboembolism: identification and biodistribution of the principal radiolabeled metabolite","volume":"34","author":"Edwards","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"2020052004581482800_jez207-B12","first-page":"18771.","article-title":"Protease-activated receptor type 4 (PAR-4) antagonism with BMS-986120 selectively inhibits human thrombus formation under conditions of high shear stress","volume":"134","author":"Wilson","year":"2016","journal-title":"Circulation"},{"key":"2020052004581482800_jez207-B13","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.thromres.2010.06.030","article-title":"Characterisation and reproducibility of a human ex vivo model of thrombosis","volume":"126","author":"Lucking","year":"2010","journal-title":"Thromb Res"},{"key":"2020052004581482800_jez207-B14","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1161\/ATVBAHA.112.300395","article-title":"Endogenous tissue plasminogen activator enhances fibrinolysis and limits thrombus formation in a clinical model of thrombosis","volume":"33","author":"Lucking","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020052004581482800_jez207-B15","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1161\/CIRCULATIONAHA.110.987263","article-title":"Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men","volume":"123","author":"Lucking","year":"2011","journal-title":"Circulation"},{"key":"2020052004581482800_jez207-B16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0049-3848(90)90106-M","article-title":"Rat model of arterial thrombosis induced by ferric chloride","volume":"60","author":"Kurz","year":"1990","journal-title":"Thromb Res"},{"key":"2020052004581482800_jez207-B17","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"2020052004581482800_jez207-B18","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/j.thromres.2014.03.017","article-title":"Fibrinogen and red blood cells in venous thrombosis","volume":"133","author":"Aleman","year":"2014","journal-title":"Thromb Res"},{"key":"2020052004581482800_jez207-B19","first-page":"406","article-title":"The role of molecular imaging in diagnosis of deep vein thrombosis","volume":"4","author":"Houshmand","year":"2014","journal-title":"Am J Nucl Med Mol Imaging"},{"key":"2020052004581482800_jez207-B20","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1182\/blood-2015-09-672188","article-title":"A systems approach to hemostasis: 4. How hemostatic thrombi limit the loss of plasma-borne molecules from the microvasculature","volume":"127","author":"Welsh","year":"2016","journal-title":"Blood"},{"key":"2020052004581482800_jez207-B21","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1124\/dmd.106.014126","article-title":"NC100668, a new tracer tested for imaging of venous thromboembolism: pharmacokinetics and metabolism in humans","volume":"35","author":"Toft","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"2020052004581482800_jez207-B22","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.2967\/jnumed.115.160754","article-title":"Multimodal molecular imaging reveals high target uptake and specificity of 111In- and 68Ga-labeled fibrin-binding probes for thrombus detection in rats","volume":"56","author":"Oliveira","year":"2015","journal-title":"J Nucl Med"},{"key":"2020052004581482800_jez207-B23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.cpet.2007.08.001","article-title":"Advances in PET image reconstruction","volume":"2","author":"Reader","year":"2007","journal-title":"PET Clin"},{"key":"2020052004581482800_jez207-B24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/MNM.0b013e3282f3a515","article-title":"PET versus SPECT: strengths, limitations and challenges","volume":"29","author":"Rahmim","year":"2008","journal-title":"Nucl Med Commun"},{"key":"2020052004581482800_jez207-B25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jlcr.3161","article-title":"Al(18) F labeling of peptides and proteins","volume":"57","author":"Laverman","year":"2014","journal-title":"J Labelled Comp Radiopharm"},{"key":"2020052004581482800_jez207-B26","article-title":"Ferric chloride-induced murine thrombosis models","volume":"115","author":"Li","year":"2016","journal-title":"J Vis Exp"},{"key":"2020052004581482800_jez207-B27","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1148\/radiol.10100881","article-title":"Bimodal thrombus imaging: simultaneous PET\/MR imaging with a fibrin-targeted dual PET\/MR probe\u2013feasibility study in rat model","volume":"258","author":"Uppal","year":"2011","journal-title":"Radiology"},{"key":"2020052004581482800_jez207-B28","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/10520290701567916","article-title":"Macromolecular changes caused by formalin fixation and antigen retrieval","volume":"82","author":"Dapson","year":"2007","journal-title":"Biotech Histochem"},{"key":"2020052004581482800_jez207-B29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1182\/blood-2014-08-594754","article-title":"Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation and bone erosion","volume":"125","author":"Raghu","year":"2015","journal-title":"Blood"},{"key":"2020052004581482800_jez207-B30","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1161\/ATVBAHA.115.306055","article-title":"Multisite thrombus imaging and fibrin content estimation with a single whole-body PET scan in rats","volume":"35","author":"Blasi","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020052004581482800_jez207-B31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1749-6632.1992.tb51627.x","article-title":"Composition and susceptibility to thrombolysis of pathological human arterial thrombi","volume":"667","author":"Brommer","year":"1992","journal-title":"Ann N Y Acad Sci"},{"key":"2020052004581482800_jez207-B32","doi-asserted-by":"crossref","first-page":"6216","DOI":"10.1158\/0008-5472.CAN-14-0594","article-title":"Pretargeted dual-modality immuno-SPECT and near-infrared fluorescence imaging for image-guided surgery of prostate cancer","volume":"74","author":"L\u00fctje","year":"2014","journal-title":"Cancer Res"},{"key":"2020052004581482800_jez207-B33","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s11307-014-0747-y","article-title":"Targeted radionuclide and fluorescence dual-modality imaging of cancer: preclinical advances and clinical translation","volume":"16","author":"L\u00fctje","year":"2014","journal-title":"Mol Imaging Biol"},{"key":"2020052004581482800_jez207-B34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2967\/jnumed.116.176099","article-title":"Dual-modality imaging of prostate cancer with a fluorescent and radiogallium-labeled gastrin-releasing peptide receptor antagonist","volume":"58","author":"Zhang","year":"2017","journal-title":"J Nucl Med"}],"container-title":["European Heart Journal - Cardiovascular Imaging"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ehjcimaging\/article-pdf\/21\/6\/673\/33238733\/jez207.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ehjcimaging\/article-pdf\/21\/6\/673\/33238733\/jez207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T08:59:59Z","timestamp":1589965199000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcimaging\/article\/21\/6\/673\/5549420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,13]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,8,13]]},"published-print":{"date-parts":[[2020,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjci\/jez207","relation":{},"ISSN":["2047-2404","2047-2412"],"issn-type":[{"value":"2047-2404","type":"print"},{"value":"2047-2412","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6]]},"published":{"date-parts":[[2019,8,13]]}}}