title: PET/CT and MR imaging biomarker of lipid-rich plaques using [64Cu]-labeled scavenger receptor (CD68-Fc).
abstract: Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE(-/-)) mice (n = 6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n = 6). Positron emission tomography (PET) with an acquisition time of 1800 s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50 µl (64)Cu-CD68-Fc (~20-30 µg labeled protein/mouse containing approximately 10-12 MBq (64)Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23 mm). Enhanced (64)Cu-CD68-Fc uptake was found in the aortic arches of ApoE(-/-) compared to WT mice (ApoE(-/-) mice:10.5 ± 1.5 Bq/cm(3) vs. WT mice: 2.1 ± 0.3 Bq/cm(3); P = 0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE(-/-) compared to WT mice using R(1) maps (R(1) = 1.47 ± 0.06 s(-1) vs. 0.92 ± 0.05 s(-1); P <0.001). Radiolabeled scavenger receptor ((64)Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification.
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom; Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik für Kardiologie und Pulmologie, Berlin, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom.
authors.forename: Alkystis
authors.initials: A
authors.lastname: Phinikaridou
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom; Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Chile.
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Andia
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Cooper
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom; Department of Cardiology and Pulmonology, Georg-August-University, Göttingen, Germany; Department of Cardiology and Pulmonology, German Centre for Cardiovascular Research (DZHK Partner Site), Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schuster
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurster
authors.affiliation: Lantheus Medical Imaging, North Billerica, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Onthank
authors.affiliation: AdvanceCor GmbH, Martinsried, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Münch
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Blower
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom; BHF Centre of Excellence, King's College London, United Kingdom; Wellcome Trust and EPSRC Medical Engineering Center, King's College London, United Kingdom; NIHR Biomedical Research Centre, King's College London, London, United Kingdom.
authors.forename: Eike
authors.initials: E
authors.lastname: Nagel
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom; AdvanceCor GmbH, Martinsried, Germany; Wellcome Trust and EPSRC Medical Engineering Center, King's College London, United Kingdom; NIHR Biomedical Research Centre, King's College London, London, United Kingdom. Electronic address: rene.botnar@kcl.ac.uk.
authors.forename: Rene M
authors.initials: RM
authors.lastname: Botnar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D051116:Receptors, Scavenger / Q000378:metabolism*; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003301:Copper Radioisotopes; D051116:Receptors, Scavenger; C081026:CD68 protein, mouse; D000097382:CD68 Molecule
keywords: (64)Cu-labeled CD68-Fc; ApoE(−/−) mice; Atherosclerosis; Imaging biomarker of plaque erosion; PET/CT and MRI