Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease

• Published in: Nature communications Vol. 8; no. 1; p. 14064
• Main Authors: Keliher, Edmund J., Ye, Yu-Xiang, Wojtkiewicz, Gregory R., Aguirre, Aaron D., Tricot, Benoit, Senders, Max L., Groenen, Hannah, Fay, Francois, Perez-Medina, Carlos, Calcagno, Claudia, Carlucci, Giuseppe, Reiner, Thomas, Sun, Yuan, Courties, Gabriel, Iwamoto, Yoshiko, Kim, Hye-Yeong, Wang, Cuihua, Chen, John W., Swirski, Filip K., Wey, Hsiao-Ying, Hooker, Jacob, Fayad, Zahi A., Mulder, Willem J. M., Weissleder, Ralph, Nahrendorf, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-01-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 59; 59/78; 631/1647/245/2092; 631/61/24; 692/4019/592/75; 692/698/1543/1565/342; Animals; Atherosclerosis; Biology; Cardiovascular disease; Female; Fluorine Radioisotopes - chemistry; Fluorine Radioisotopes - metabolism; Glucans - chemistry; Glucans - metabolism; Heart - diagnostic imaging; Heart attacks; Hospitals; Humanities and Social Sciences; Humans; Ischemia; Macrophages - chemistry; Macrophages - metabolism; Magnetic resonance imaging; Male; Medical schools; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Myocardial Ischemia - diagnostic imaging; Myocardial Ischemia - metabolism; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Positron-Emission Tomography - instrumentation; Positron-Emission Tomography - methods; Rabbits; Renal Elimination; Science; Science (multidisciplinary); Tomography; New York; United States > US; Massachusetts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14064

Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with
18
F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18. The particle’s short blood half-life, measured in three species, including a primate, enables macrophage imaging in inflamed cardiovascular tissues. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. In PET/magnetic resonance imaging (MRI) experiments, Macroflor PET imaging detects changes in macrophage population size while molecular MRI reports on increasing or resolving inflammation. These data suggest that Macroflor PET/MRI could be a clinical tool to non-invasively monitor macrophage biology.
In vivo
imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher
et al
. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.