{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:14:13Z","timestamp":1790054053463,"version":"4.0.1"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["675417 PET3D"],"award-info":[{"award-number":["675417 PET3D"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G005815N"],"award-info":[{"award-number":["G005815N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0D8817N"],"award-info":[{"award-number":["G0D8817N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (&gt;75%) and radiochemical purity (&gt;99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE\u2212\/\u2212 mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET\/CT systems and finally sacrificed for ex vivo analysis. Both the PET\/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the \u03b2-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.<\/jats:p>","DOI":"10.3390\/molecules25081838","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"1838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-9763","authenticated-orcid":false,"given":"Jessica","family":"Bridoux","sequence":"first","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Neyt","sequence":"additional","affiliation":[{"name":"Preclinical imaging, MOLECUBES NV, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-7814","authenticated-orcid":false,"given":"Pieterjan","family":"Debie","sequence":"additional","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicte","family":"Descamps","sequence":"additional","affiliation":[{"name":"IBiTech-MEDISIP, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-4833","authenticated-orcid":false,"given":"Nick","family":"Devoogdt","sequence":"additional","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Cleeren","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Bormans","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4265-8463","authenticated-orcid":false,"given":"Alexis","family":"Broisat","sequence":"additional","affiliation":[{"name":"Radiopharmaceutiques Biocliniques, INSERM 1039, Universit\u00e9 de Grenoble, 38400 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Caveliers","sequence":"additional","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Nuclear Medicine department, UZ Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-1074","authenticated-orcid":false,"given":"Catarina","family":"Xavier","sequence":"additional","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3988-5980","authenticated-orcid":false,"given":"Christian","family":"Vanhove","sequence":"additional","affiliation":[{"name":"IBiTech-MEDISIP, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Hernot","sequence":"additional","affiliation":[{"name":"Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"Lusis","year":"2018","journal-title":"Nature"},{"key":"ref_2","unstructured":"World Health Organization (2020, April 15). The Top 10 Causes of Death. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/the-top-10-causes-of-death."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European Guidelines on cardiovascular disease prevention in clinical practice, Joint ESC Guidelines","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.atherosclerosis.2012.12.017","article-title":"Determinants of calcification growth in atherosclerotic carotid arteries; a serial multi-detector CT angiography study","volume":"227","author":"Bodde","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guaricci, A.I., De Santis, D., Carbone, M., Muscogiuri, G., Guglielmo, M., Baggiano, A., and Serviddio, G. (2018). Coronary Atherosclerosis Assessment by Coronary CT Angiography in Asymptomatic Diabetic Population: A Critical Systematic Review of the Literature and Future Perspectives. Biomed. Res. Int., 2018.","DOI":"10.1155\/2018\/8927281"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s40477-017-0239-4","article-title":"Contrast-enhanced ultrasound of the carotid system: A review of the current literature","volume":"20","author":"Rafailidis","year":"2017","journal-title":"J. Ultrasound"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1080\/17434440.2017.1407646","article-title":"What does the future hold for novel intravascular imaging devices: A focus on morphological and physiological assessment of plaque","volume":"14","author":"Katagiri","year":"2017","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.atherosclerosis.2016.06.028","article-title":"Non-invasive imaging of atherosclerosis regression with magnetic resonance to guide drug development","volume":"251","author":"Raggi","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s40134-016-0141-4","article-title":"The Role of MRI and CT in the Diagnosis of Atherosclerosis in an Aging Population","volume":"4","author":"Eid","year":"2016","journal-title":"Curr. Radiol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1097\/CRD.0000000000000128","article-title":"A Review of the Clinical Utility of Intravascular Ultrasoundand Optical Coherence Tomography in the Assessment and Treatment of Coronary Artery Disease","volume":"25","author":"Matthews","year":"2017","journal-title":"Cardiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11883-016-0584-3","article-title":"PET Imaging of Atherosclerostic Disease: Advancing Plaque Assessment from Anatomy to Pathophysiology","volume":"18","author":"Evans","year":"2016","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphy.2014.00012","article-title":"Quantitative preclinical PET imaging: Opportunities and challenges","volume":"2","author":"Kuntner","year":"2014","journal-title":"Front. Phys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155013","DOI":"10.1088\/1361-6560\/aacec3","article-title":"Performance evaluation of the MOLECUBES b-CUBE\u2014a high special resolution and high sensitivity small animal PET scanner utilizing monolithic LYSO scintillation detectors","volume":"63","author":"Krishnamoorthy","year":"2018","journal-title":"Phys. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1161\/CIRCRESAHA.112.265140","article-title":"Nanobodies targeting mouse\/human VCAM1 for the nuclear imaging of atherosclerotic lesions","volume":"110","author":"Broisat","year":"2012","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.jcmg.2018.07.027","article-title":"Nanobody-Facilitated Multiparametric PET\/MRI Phenotyping of Atherosclerosis","volume":"12","author":"Senders","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"386","DOI":"10.7150\/thno.8006","article-title":"Nanobody: The \u00ab Magic Bullet \u00bb for Molecular Imaging?","volume":"4","author":"Chakravarty","year":"2014","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Debie, P., Devoogdt, N., and Hernot, S. (2019). Targeted Nanobody-Based Molecular Tracers for Nuclear Imaging and Image-Guided Surgery. Antibodies, 8.","DOI":"10.3390\/antib8010012"},{"key":"ref_18","unstructured":"Musthakahmed, A.M.S., Billaud, E., Bormans, G.M., Cleeren, F., Lecina, J., and Verbruggen, A. (2020, April 15). Methods for low temperature fluorine-18 radiolabelling of biomolecules (WO\/216\/065435). Available online: patents.google.com."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1038\/s41596-018-0040-7","article-title":"Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method","volume":"13","author":"Cleeren","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.7150\/thno.20094","article-title":"Al18F-Labelling of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging","volume":"14","author":"Cleeren","year":"2017","journal-title":"Theranostics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1053\/j.semnuclmed.2008.01.001","article-title":"Technological Development and Advances in SPECT\/CT","volume":"38","author":"Seo","year":"2008","journal-title":"Semin. Nucl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1093\/ehjci\/jev346","article-title":"Targeting of vascular cell adhesion molecule-1 by 18F-labelled nanobodies for PET\/CT imaging of inflamed atherosclerotic plaques","volume":"17","author":"Bala","year":"2016","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1515\/hsz-2018-0330","article-title":"Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis \u2013 impact of radiochemistry on pharmacokinetics","volume":"400","author":"Bala","year":"2019","journal-title":"Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.nucmedbio.2016.01.002","article-title":"(18)F-nanobody for PET imaging of HER2 overexpressing tumors","volume":"43","author":"Xavier","year":"2016","journal-title":"Nucl. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.molimm.2006.08.021","article-title":"VCAM-1-positive stromal cells from human bone marrow producing cytokines for B lineage progenitors and for plasma cells: SDF-1, flt3L, and BAFF","volume":"44","author":"Schaumann","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"537697","DOI":"10.1155\/2011\/537687","article-title":"Advances in Drug Design of Radiometal-Based Imaging Agents for Bone Disorders","volume":"2011","author":"Ogawa","year":"2011","journal-title":"Int. J. Mol. Imaging."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"van der Veen, E.L., Suurs, F.V., Cleeren, F., Bormans, G., Elsinga, P.H., Hospers, G.A.P., Lub-de Hooge, M.N., de Vries, E.F.J., and Antunes, I. (2020). Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice. JNM.","DOI":"10.2967\/jnumed.119.238782"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.21037\/qims.2018.01.02","article-title":"Site specific mesurements of bone formation using [18F] sodium fluoride PET\/CT","volume":"8","author":"Blake","year":"2018","journal-title":"Quant. Imaging Med. Surg."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:44:52Z","timestamp":1760363092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["molecules25081838"],"URL":"https:\/\/doi.org\/10.3390\/molecules25081838","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}