title: Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer68Ga-Pentixafor for PET.
abstract: 68Ga-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model.Methods:Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of68Ga-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of125I-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections.Results:One hour after injection of68Ga-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively;P< 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced125I-pentixafor uptake in atherosclerotic plaques by approximately 40%.125I-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r2= 0.61;P< 0.05).Conclusion:68Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to18F-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany fabien.hyafil@gmail.com.|Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Inserm 1148, DHU FIRE, University Diderot, Paris, France.
authors: Fabien
authors: F
authors: Hyafil
authors: Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors: Jaroslav
authors: J
authors: Pelisek
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany.
authors: Iina
authors: I
authors: Laitinen
authors: Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
authors: Margret
authors: M
authors: Schottelius
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany.
authors: Miriam
authors: M
authors: Mohring
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Yvonne
authors: Y
authors: Döring
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Emiel P C
authors: EP
authors: van der Vorst
authors: Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors: Michael
authors: M
authors: Kallmayer
authors: Institute of Pathology, Technische Universität München, Munich, Germany.
authors: Katja
authors: K
authors: Steiger
authors: Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
authors: Andreas
authors: A
authors: Poschenrieder
authors: Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
authors: Johannes
authors: J
authors: Notni
authors: Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.
authors: Johannes
authors: J
authors: Fischer
authors: Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.
authors: Christine
authors: C
authors: Baumgartner
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany.|Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Inserm 1148, DHU FIRE, University Diderot, Paris, France.|Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.|Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.|Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.|Institute of Pathology, Technische Universität München, Munich, Germany.|Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) partner site Munich Heart Alliance, Munich, Germany; and.
authors: Christoph
authors: C
authors: Rischpler
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany.|Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Inserm 1148, DHU FIRE, University Diderot, Paris, France.|Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.|Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.|Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.|Institute of Pathology, Technische Universität München, Munich, Germany.|Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) partner site Munich Heart Alliance, Munich, Germany; and.
authors: Stephan G
authors: SG
authors: Nekolla
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.|Institute of Pathology, Technische Universität München, Munich, Germany.|Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) partner site Munich Heart Alliance, Munich, Germany; and.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors: Christian
authors: C
authors: Weber
authors: Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors: Hans-Henning
authors: HH
authors: Eckstein
authors: Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
authors: Hans-Jürgen
authors: HJ
authors: Wester
authors: Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany.|Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Inserm 1148, DHU FIRE, University Diderot, Paris, France.|Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany.|Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.|Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.|Institute of Pathology, Technische Universität München, Munich, Germany.|Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) partner site Munich Heart Alliance, Munich, Germany; and.
authors: Markus
authors: M
authors: Schwaiger
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D056831:Coordination Complexes / Q000493:pharmacokinetics*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D054387:Receptors, CXCR / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C000597686:68Ga-pentixafor; D056831:Coordination Complexes; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D054387:Receptors, CXCR
keywords: CXCR4; PET; atherosclerosis; inflammation; macrophages; radiotracer