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Published on: December 18, 2020
Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64Cu-Macrin in Mice,
Matthias Nahrendorf1,2,3,4, Friedrich Felix Hoyer1,2, Anu E Meerwaldt5,6
1Center for Systems Biology (M.N., F.F.H., D.R., A.D.A., G.W., S.S., Y.I., F.K.S., R.W.), Massachusetts General Hospital Research Institute and Harvard Medical School, Boston.
Background:
Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases.
Methods:
We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64Cu-Macrin-a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose.
Results:
PET imaging using 64Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle (VT680Macrin) primarily in tissue macrophages. In 5-day-old mice, 64Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of 64Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that 64Cu-Macrin is safe for use in humans.
Conclusions:
Taken together, these results indicate 64Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. 64Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.
Insights
A new nanoparticle, 64Cu-Macrin, allows noninvasive imaging of macrophages in organs like the heart and lungs. This tool can track inflammatory responses in cardiovascular diseases and assess macrophage-targeted therapies.
Area of Science:
- Immunology
- Nanotechnology
- Medical Imaging
Background:
- Macrophages are key innate immune cells involved in host defense.
- Inflammatory macrophages contribute to cardiovascular disease progression in the heart and vasculature.
Purpose of the Study:
- To evaluate the quantitative, noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64Cu-Macrin.
- To assess the safety and efficacy of 64Cu-Macrin for imaging macrophage dynamics.
Main Methods:
- In vivo positron emission tomography (PET) imaging with 64Cu-Macrin.
- Flow cytometry and confocal microscopy using a fluorescent version of the nanoparticle (VT680Macrin).
- Toxicity studies in rats and human dosimetry estimates.
Main Results:
- 64Cu-Macrin PET accurately detected macrophage accumulation in the heart and lungs of mice with various conditions.
- Nanoparticle detected macrophages in cardiac, pulmonary, and vascular tissues in preclinical animal models (rabbits, pigs).
- Toxicity studies indicated 64Cu-Macrin is safe for human use.
Conclusions:
- 64Cu-Macrin serves as a versatile PET nanotracer for surveying macrophage dynamics in physiological and pathological states.
- 64Cu-Macrin PET imaging can stage inflammatory cardiovascular disease activity and aid in disease management.
- This nanotracer shows potential as an imaging biomarker for macrophage-targeted therapeutics.
