1. Detection of macrophages in aortic aneurysms by nanoparticle positron emission tomography-computed tomography.
- Author
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Nahrendorf M, Keliher E, Marinelli B, Leuschner F, Robbins CS, Gerszten RE, Pittet MJ, Swirski FK, and Weissleder R
- Subjects
- Angiotensin II, Animals, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal etiology, Aortic Aneurysm, Abdominal immunology, Apolipoproteins E deficiency, Apolipoproteins E genetics, Autoradiography, Disease Models, Animal, Female, Flow Cytometry, Macrophages immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes diagnostic imaging, Predictive Value of Tests, Reproducibility of Results, Splenectomy, Time Factors, Aortic Aneurysm, Abdominal diagnosis, Contrast Media, Fluorodeoxyglucose F18, Macrophages diagnostic imaging, Metal Nanoparticles, Positron-Emission Tomography, Radiopharmaceuticals, X-Ray Microtomography
- Abstract
Objective: Current management of aortic aneurysms (AAs) relies primarily on size criteria to determine whether invasive repair is indicated to preempt rupture. We hypothesized that emerging molecular imaging tools could be used to more sensitively gauge local inflammation. Because macrophages are key effector cells that destabilize the extracellular matrix in the arterial wall, it seemed likely that they would represent suitable imaging targets. We here aimed to develop and validate macrophage-targeted nanoparticles labeled with fluorine-18 ((18)F) for positron emission tomography-computed tomography (PET-CT) detection of inflammation in AAs., Methods and Results: Aneurysms were induced in apolipoprotein E-/- mice via systemic administration of angiotensin II. Mice were imaged using PET-CT and a monocyte/macrophage-targeted nanoparticle. AAs were detected by contrast-enhanced micro-CT and had a mean diameter of 1.85 ± 0.08 mm, whereas normal aortas measured 1.07 ± 0.03 (P < 0.05). The in vivo PET signal was significantly higher in aneurysms (standard uptake value, 2.46 ± 0.48) compared with wild-type aorta (0.82 ± 0.05, P < 0.05). Validation with scintillation counting, autoradiography, fluorescence, and immunoreactive histology and flow cytometry demonstrated that nanoparticles localized predominantly to monocytes and macrophages within the aneurysmatic wall., Conclusions: PET-CT imaging with (18)F-labeled nanoparticles allows quantitation of macrophage content in a mouse model of AA.
- Published
- 2011
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