Dataset Information

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor ⁶⁴Cu-Macrin in Mice, Rabbits, and Pigs.

ABSTRACT:

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.

SUBMITTER: Nahrendorf M

PROVIDER: S-EPMC7583675 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor <sup>64</sup>Cu-Macrin in Mice, Rabbits, and Pigs.

Nahrendorf Matthias M Hoyer Friedrich Felix FF Meerwaldt Anu E AE van Leent Mandy M T MMT Senders Max L ML Calcagno Claudia C Robson Philip M PM Soultanidis George G Pérez-Medina Carlos C Teunissen Abraham J P AJP Toner Yohana C YC Ishikawa Kiyotake K Fish Kenneth K Sakurai Ken K van Leeuwen Esther M EM Klein Emma D ED Sofias Alexandros Marios AM Reiner Thomas T Rohde David D Aguirre Aaron D AD Wojtkiewicz Gregory G Schmidt Stephen S Iwamoto Yoshiko Y Izquierdo-Garcia David D Caravan Peter P Swirski Filip K FK Weissleder Ralph R Mulder Willem J M WJM

Circulation. Cardiovascular imaging 20201020 10

<h4>Background</h4>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.<h4>Methods</h4>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 <sup>64</sup>Cu-Macri ...[more]

PMID: 33076700

Similar Datasets

Project description:H2dedpa-N,N'-pram (H2L1), a new chelator derived from the hexadentate ligand 1,2-bis[[(6-carboxypyridin-2-yl)methyl]amino]ethane (H2dedpa), which incorporates 3-propylamine chains anchored to the secondary amines of the ethylenediamine core of the latter, has emerged as a very promising scaffold for preparing 68Ga- and 64Cu-based positron emission tomography probes. This new platform is cost-effective and easy to prepare, and the two pendant primary amines make it versatile for the preparation of bifunctional chelators by conjugation and/or click chemistry. Reported herein, we have also included the related H2dedpa-N,N'-prpta (H2L2) platform as a simple structural model for its conjugated systems. X-ray crystallography confirmed that the N4O2 coordination sphere provided by the dedpa2- core is maintained at both Ga(III) and Cu(II). The complex formation equilibria were deeply investigated by a thorough multitechnique approach with potentiometric, NMR spectrometric, and UV-vis spectrophotometric titrations, revealing effective chelation. The thermodynamic stability of the Ga(III) complexes at physiological relevant conditions is slightly higher than that of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the common and clinically approved chelator used in the clinic [pGa = 19.5 (dedpa-N,N'-pram) and 20.8 (dedpa-N,N'-prpta) versus 18.5 (DOTA) at identical conditions], and significantly higher for the Cu(II) complexes [pCu = 21.96 (dedpa-N,N'-pram) and 22.8 (dedpa-N,N'-prpta) versus 16.2 (DOTA)], which are even more stable than that of the parent ligand dedpa2- (pCu = 18.5) and that of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) (pCu = 18.5). This high stability found for Cu(II) complexes is related to the conversion of the secondary amines of the ethylenediamine core of dedpa2- into tertiary amines, whereby the architecture of the new H2L1 chelator is doubly optimal in the case of this metal ion: high accessibility of the primary amine groups and their incorporation via the secondary amines, which contributes to a significant increase in the stability of the metal complex. Quantitative labeling of both chelators with both radionuclides ([68Ga]Ga3+ and [64Cu]Cu2+) was observed within 15 min at room temperature with concentrations as low as 10-5 M. Furthermore, serum stability studies confirmed a high radiochemical in vitro stability of all systems and therefore confirmed H2L1 as a promising and versatile chelator for further radiopharmaceutical in vivo studies.

Dataset Information

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor ⁶⁴Cu-Macrin in Mice, Rabbits, and Pigs.

Background

Methods

Results

Conclusions

Publications

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor <sup>64</sup>Cu-Macrin in Mice, Rabbits, and Pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64Cu-Macrin in Mice, Rabbits, and Pigs.

Background

Methods

Results

Conclusions

Publications

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor <sup>64</sup>Cu-Macrin in Mice, Rabbits, and Pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor ⁶⁴Cu-Macrin in Mice, Rabbits, and Pigs.