Detection of macrophages in aortic aneurysms by nanoparticle positron emission tomography-computed tomography.
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.


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.
Center for Systems Biology, 185 Cambridge St, Boston, MA 02114, USA. mnahrendorf@mgh.harvard.edu
Matthias
M
Nahrendorf
Edmund
E
Keliher
Brett
B
Marinelli
Florian
F
Leuschner
Clinton S
CS
Robbins
Robert E
RE
Gerszten
Mikael J
MJ
Pittet
Filip K
FK
Swirski
Ralph
R
Weissleder
D000804:Angiotensin II; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001345:Autoradiography; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D008264:Macrophages / Q000000981:diagnostic imaging* / Q000276:immunology; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D013156:Splenectomy; D013997:Time Factors; D055114:X-Ray Microtomography
D001057:Apolipoproteins E; D003287:Contrast Media; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000804:Angiotensin II
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