Author + information
- Received June 20, 2017
- Revision received October 16, 2017
- Accepted November 1, 2017
- Published online February 5, 2018.
- Claudia Calcagno, MD, PhDa,b,
- Olivier Lairez, MD, PhDa,b,c,
- Julie Hawkins, PhDd,
- Steven W. Kerr, BS, MSd,
- Melanie S. Dugas, BSd,
- Thomas Simpson, PhDe,
- Jelle Epskamp, MDf,
- Philip M. Robson, PhDa,b,
- Mootaz Eldib, PhDa,b,
- Ilda Bander, MDa,b,
- Purushothaman K-Raman, MDg,
- Sarayu Ramachandran, MSa,b,
- Alison Pruzan, ScBa,b,
- Audrey Kaufman, MDa,b,
- Venkatesh Mani, PhDa,b,
- Alexander Ehlgen, MDh,
- Heiko G. Niessen, PhDh,
- John Broadwater, PhDd and
- Zahi A. Fayad, PhDa,b,∗ ()
- aTranslational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bDepartment of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
- cDepartment of Cardiology and Cardiac Imaging Center, Rangueil University Hospital, Toulouse, France
- dDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut
- eDepartment of Chemistry, West Chester University, West Chester, Pennsylvania
- fAcademisch Medisch Centrum, Amsterdam, the Netherlands
- gDepartment of Cardiology, Icahn School of Medicine at Mount Sinai New York, New York
- hDepartment of Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- ↵∗Address for correspondence:
Dr. Zahi A. Fayad, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029.
Objectives The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis.
Background Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751.
Methods New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study.
Results Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups.
Conclusions The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.
Dr. Calcagno is supported by a Scientist Development Grant from the American Heart Association (16SDG27250090). Dr. Lairez was supported in part by grants from the Fédération Française de Cardiologie. Drs. Calcagno, Robson, Eldib, Mani, and Fayad are supported by NIH grants EB009638, HL071021 and HL128056. Drs. Hawkins, Kerr, Dugas, and Broadwater are employees of Boehringer Ingelheim Pharmaceuticals, Inc. Dr. Simpson is a former employee of Boehringer Ingelheim. Drs. Ehlgen and Niessen are employees of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Calcagno and Lairez contributed equally to this paper and are joint first authors. Heinrich R. Schelbert, MD, served as the Guest Editor for this paper.
- Received June 20, 2017.
- Revision received October 16, 2017.
- Accepted November 1, 2017.
- 2018 American College of Cardiology Foundation
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