TY - JOUR
T1 - Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64Cu-Macrin in Mice, Rabbits, and Pigs
AU - Nahrendorf, Matthias
AU - Hoyer, Friedrich Felix
AU - Meerwaldt, Anu E.
AU - van Leent, Mandy M.T.
AU - Senders, Max L.
AU - Calcagno, Claudia
AU - Robson, Philip M.
AU - Soultanidis, George
AU - Pérez-Medina, Carlos
AU - Teunissen, Abraham J.P.
AU - Toner, Yohana C.
AU - Ishikawa, Kiyotake
AU - Fish, Kenneth
AU - Sakurai, Ken
AU - van Leeuwen, Esther M.
AU - Klein, Emma D.
AU - Sofias, Alexandros Marios
AU - Reiner, Thomas
AU - Rohde, David
AU - Aguirre, Aaron D.
AU - Wojtkiewicz, Gregory
AU - Schmidt, Stephen
AU - Iwamoto, Yoshiko
AU - Izquierdo-Garcia, David
AU - Caravan, Peter
AU - Swirski, Filip K.
AU - Weissleder, Ralph
AU - Mulder, Willem J.M.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - heart
KW - macrophages
KW - myocardial infarction
KW - nanoparticles
KW - pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85093910684&partnerID=8YFLogxK
U2 - 10.1161/CIRCIMAGING.120.010586
DO - 10.1161/CIRCIMAGING.120.010586
M3 - Article
C2 - 33076700
AN - SCOPUS:85093910684
SN - 1941-9651
VL - 13
SP - e010586
JO - Circulation. Cardiovascular Imaging
JF - Circulation. Cardiovascular Imaging
IS - 10
M1 - e010586
ER -