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MRI Tracking of Macrophages Labeled with Glucan Particles Entrapping a Water Insoluble Paramagnetic Gd-Based Agent

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Abstract

Purpose

This study is aimed at demonstrating the in vivo potential of Gd(III)-loaded glucan particles (Gd-GPs) as magnetic resonance imaging (MRI)-positive agents for labeling and tracking phagocytic cells.

Procedure

GPs were obtained from Saccharomyces cerevisae and loaded with the water-insoluble complex Gd-DOTAMA(C18)2. The uptake kinetics of Gd-GPs by murine macrophages was studied in vitro and the internalization mechanism was assessed by competition assays. The in vivo performance of Gd-GPs was tested at 7.05 T on a mouse model of acute liver inflammation.

Results

The minimum number of Gd-GPs-labeled J774.A1 macrophages detected in vitro by MRI was ca. 300 cells/μl of agar, which is the lowest number ever reported for cells labeled with a positive T1 agent. Intravenous injection of macrophages labeled with Gd-GPs in a mouse model of liver inflammation enabled the MRI visualization of the cellular infiltration in the diseased area.

Conclusions

Gd-GPs represent a promising platform for tracking macrophages by MRI as a T1 alternative to the golden standard T2-based iron oxide particles.

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Abbreviations

Gd-GPs:

Gd-loaded glucan particles

GPs:

Glucan particles

Rho:

GPs rhodamine-loaded glucan particles

PBS:

Phosphate-buffered saline

ALT:

Alanine amino transferase

USPIO:

Ultra-small superparamagnetic iron oxide particles

SPIO:

Superparamagnetic iron oxide particles

MPIO:

Micrometer-sized iron oxide particles

siRNA:

Small interfering RNA

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Acknowledgments

The authors thank Regione Piemonte (PIIMDMT and nano-IGT projects), Foundation for Science and Technology of Portugal (project PTDC/QUI/70063/2006, contract REDE/1517/RMN/2005, and grant No. SFRH/BD/33187/2007 to SF) and FEDER, for their support. This work was carried out in the framework of the EU COST D38 and TD1004 Actions and EU-FP7 projects ENCITE (grant No. 201842) and INMiND (grant No. 278850).

Conflict of Interest

Dr. Terreno and Dr. Aime are consultants for Bracco Imaging S.p.A. The other authors have no potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Molecular Biotechnology and Health Sciences and Molecular and Preclinical Imaging Centers, University of Turin, Turin, Italy

    Sara Figueiredo, Juan Carlos Cutrin, Silvia Rizzitelli, Elisa De Luca, Silvio Aime & Enzo Terreno

  2. ININCA (UBA-CONICET), Buenos Aires, Argentina

    Juan Carlos Cutrin

  3. FFUC-Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    João Nuno Moreira

  4. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal

    Sara Figueiredo & Carlos F. G. C. Geraldes

  5. CNC-Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal

    Sara Figueiredo, João Nuno Moreira & Carlos F. G. C. Geraldes

  6. Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal

    Carlos F. G. C. Geraldes

Authors
  1. Sara Figueiredo
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Correspondence to Enzo Terreno.

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Figueiredo, S., Cutrin, J.C., Rizzitelli, S. et al. MRI Tracking of Macrophages Labeled with Glucan Particles Entrapping a Water Insoluble Paramagnetic Gd-Based Agent. Mol Imaging Biol 15, 307–315 (2013). https://doi.org/10.1007/s11307-012-0603-x

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