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Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis.
Senders, Max L; Hernot, Sophie; Carlucci, Giuseppe; van de Voort, Jan C; Fay, Francois; Calcagno, Claudia; Tang, Jun; Alaarg, Amr; Zhao, Yiming; Ishino, Seigo; Palmisano, Anna; Boeykens, Gilles; Meerwaldt, Anu E; Sanchez-Gaytan, Brenda L; Baxter, Samantha; Zendman, Laura; Lobatto, Mark E; Karakatsanis, Nicolas A; Robson, Philip M; Broisat, Alexis; Raes, Geert; Lewis, Jason S; Tsimikas, Sotirios; Reiner, Thomas; Fayad, Zahi A; Devoogdt, Nick; Mulder, Willem J M; Pérez-Medina, Carlos.
Afiliación
  • Senders ML; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands.
  • Hernot S; In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
  • Carlucci G; Bernard and Irene Schwarz Center for Biomedical Imaging, New York University, New York, New York; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
  • van de Voort JC; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Fay F; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Chemistry, York College of The City University of New York, New York, New York.
  • Calcagno C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Tang J; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
  • Alaarg A; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Biomaterials Science and Technology, Technical Medical Centre. University of Twente, Enschede, the Netherlands.
  • Zhao Y; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Ishino S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Palmisano A; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Unit of Clinical Research in Radiology, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.
  • Boeykens G; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Meerwaldt AE; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Sanchez-Gaytan BL; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Baxter S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Zendman L; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Lobatto ME; Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
  • Karakatsanis NA; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Robson PM; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Broisat A; Bioclinic Radiopharmaceutics Laboratory, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S 1039, Grenoble, France.
  • Raes G; Research Group of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Inflammation Research Center, Ghent, Belgium.
  • Lewis JS; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Radiology, Weill Cornell Medical College, New York, New York; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Tsimikas S; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California-La Jolla, San Diego, California.
  • Reiner T; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Radiology, Weill Cornell Medical College, New York, New York.
  • Fayad ZA; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Devoogdt N; In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
  • Mulder WJM; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: willem.mulder@mssm.edu.
  • Pérez-Medina C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: carlos.perez-medina@mountsinai.org.
JACC Cardiovasc Imaging ; 12(10): 2015-2026, 2019 10.
Article en En | MEDLINE | ID: mdl-30343086
OBJECTIVES: This study sought to develop an integrative positron emission tomography (PET) with magnetic resonance imaging (MRI) procedure for accurate atherosclerotic plaque phenotyping, facilitated by clinically approved and nanobody radiotracers. BACKGROUND: Noninvasive characterization of atherosclerosis remains a challenge in clinical practice. The limitations of current diagnostic methods demonstrate that, in addition to atherosclerotic plaque morphology and composition, disease activity needs to be evaluated. METHODS: We screened 3 nanobody radiotracers targeted to different biomarkers of atherosclerosis progression, namely vascular cell adhesion molecule (VCAM)-1, lectin-like oxidized low-density lipoprotein receptor (LOX)-1, and macrophage mannose receptor (MMR). The nanobodies, initially radiolabeled with copper-64 (64Cu), were extensively evaluated in Apoe-/- mice and atherosclerotic rabbits using a combination of in vivo PET/MRI readouts and ex vivo radioactivity counting, autoradiography, and histological analyses. RESULTS: The 3 nanobody radiotracers accumulated in atherosclerotic plaques and displayed short circulation times due to fast renal clearance. The MMR nanobody was selected for labeling with gallium-68 (68Ga), a short-lived radioisotope with high clinical relevance, and used in an ensuing atherosclerosis progression PET/MRI study. Macrophage burden was longitudinally studied by 68Ga-MMR-PET, plaque burden by T2-weighted MRI, and neovascularization by dynamic contrast-enhanced (DCE) MRI. Additionally, inflammation and microcalcifications were evaluated by fluorine-18 (18F)-labeled fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) PET, respectively. We observed an increase in all the aforementioned measures as disease progressed, and the imaging signatures correlated with histopathological features. CONCLUSIONS: We have evaluated nanobody-based radiotracers in rabbits and developed an integrative PET/MRI protocol that allows noninvasive assessment of different processes relevant to atherosclerosis progression. This approach allows the multiparametric study of atherosclerosis and can aid in early stage anti-atherosclerosis drug trials.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Radiofármacos / Tomografía de Emisión de Positrones / Aterosclerosis / Placa Aterosclerótica / Anticuerpos de Dominio Único / Imágenes de Resonancia Magnética Multiparamétrica Tipo de estudio: Diagnostic_studies / Guideline / Screening_studies Límite: Animals Idioma: En Revista: JACC Cardiovasc Imaging Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / DIAGNOSTICO POR IMAGEM Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Radiofármacos / Tomografía de Emisión de Positrones / Aterosclerosis / Placa Aterosclerótica / Anticuerpos de Dominio Único / Imágenes de Resonancia Magnética Multiparamétrica Tipo de estudio: Diagnostic_studies / Guideline / Screening_studies Límite: Animals Idioma: En Revista: JACC Cardiovasc Imaging Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / DIAGNOSTICO POR IMAGEM Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos