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

ABSTRACT: 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 ¹⁸F-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.

SUBMITTER: Keliher EJ

PROVIDER: S-EPMC5241815 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Keliher Edmund J EJ Ye Yu-Xiang YX Wojtkiewicz Gregory R GR Aguirre Aaron D AD Tricot Benoit B Senders Max L ML Groenen Hannah H Fay Francois F Perez-Medina Carlos C Calcagno Claudia C Carlucci Giuseppe G Reiner Thomas T Sun Yuan Y Courties Gabriel G Iwamoto Yoshiko Y Kim Hye-Yeong HY Wang Cuihua C Chen John W JW Swirski Filip K FK Wey Hsiao-Ying HY Hooker Jacob J Fayad Zahi A ZA Mulder Willem J M WJ Weissleder Ralph R Nahrendorf Matthias M

Nature communications 20170116

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 <sup>18</sup>F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for ...[more]

PMID: 28091604

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Project description:A Mn3O4 nanoparticle (NP)-based dual-modality probe has been developed for tumor positron emission tomography (PET)/magnetic resonance (MR) imaging. The dual-modality imaging probe was constructed by modifying multifunctional polyethyleneimine (PEI)-coated Mn3O4 NPs with folic acid (FA), followed with the radiolabeling with 64Cu. The formed imaging probe was utilized for PET/MR imaging of human cervical cancer mouse xenografts, which overexpress folate receptor (FR). The PEI-coated Mn3O4 NPs were synthesized using a solvothermal approach via decomposition of acetylacetone manganese. Multifunctional groups, including fluorescein isothiocyanate (FI), PEGylated FA, and NOTA chelator, were then sequentially loaded onto the surface of the amine groups of the Mn3O4 NPs. The remaining PEI amines were neutralized by the acetylation reaction. The resulting NOTA-FA-FI-PEG-PEI-Ac-Mn3O4 NPs were fully characterized and evaluated in vitro and successfully radiolabeled with 64Cu for tumor PET/MR imaging in small animals. In vivo blocking experiments were performed to determine the FR binding specificity of NPs. PET imaging results demonstrated that 64Cu-labeled Mn3O4 NPs display good tracer uptake in the FR-expressing HeLa tumors (tumor-to-muscle (T/M) ratio: 5.35 ± 0.31 at 18 h postinjection (pi)) and substantially reduced tracer uptake in the FR-blocked HeLa tumors (T/M ratio: 2.78 ± 0.68 at 18 h pi). The ex vivo data, including PET imaging and biodistribution, further confirmed the tumor binding specificity of the 64Cu-labeled Mn3O4 NPs. Moreover, the FR-targeted Mn3O4 NPs exhibited efficient T1-weighted MR imaging (MRI), leading to the precise tumor MRI at 18 h pi. PET/MR imaging with the 64Cu-NOTA-FA-FI-PEG-PEI-Ac-Mn3O4 NPs may offer a new quantitative approach to precisely measure the FR in tumors. The strategy of incorporating PEI nanotechnology into the construction of new biomaterials may be applied for the construction of novel nanoplatforms for cancer diagnosis and therapy.

Dataset Information

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

Publications

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

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