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In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide

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Abstract

Purpose

A magnetic resonance imaging contrast agent based on a tetrameric Gd-DTPA-like system linked to a fibrin-targeting peptide (Gd-F) has been designed for in vivo tumor characterization.

Procedures

Gd-F was synthesized following Fmoc-SPPS strategy. Binding was measured using soluble fibrin DD(E) fragment and a dried fibrin assay. Contrast efficiency was tested on human and mouse clots and in vivo on Neuro2A tumor model. An anti-thrombotic drug was used to evaluate Gd-F sensitivity for changes in fibrin availability at the tumor site.

Results

The high relaxivity of Gd-F (42 mM−1 s−1, per molecule) yielded a strong signal enhancement in human and murine clots. High contrast was also measured in vivo in Neuro2A tumors, with a persistent enhancement in tumor rim and stroma. Upon treatment with an anti-thrombotic drug, the contrast uptake was significantly reduced in the tumor area confirming the specificity of the probe.

Conclusions

Gd-F resulted to be an efficient probe for tumor delineation and for monitoring fibrin deposits during tumor progression and anti-thrombotic therapy.

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Acknowledgments

This research was supported by funding from AIRC Investigator Grant—IG 2013, prog. N.14565 (S.A.). ESF COST Action TD1004 is also acknowledged. The authors thank Simona Ramponi and Adriana Grotti, CRB Bracco Imaging S.p.A., for technical assistance and support with tumor model.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy

    L. Chaabane

  2. CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy

    L. Chaabane, L. Miragoli, L. Lattuada & F. Uggeri

  3. Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, Viale T. Michel 11, 15121, Alessandria, Italy

    L. Tei

  4. Bracco Research SA, Route de la Galaise, 31, 1228, Plan-les-Ouates, Geneva, Switzerland

    M. von Wronski

  5. Ephoran Multi Imaging Solutions, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy

    V. Lorusso

  6. Dipartimento di Biotecnologie Molecolari e Scienze per la Salute and Molecular Imaging Center, Università di Torino, Via Nizza 52, 10125, Torino, Italy

    S. Aime

Authors
  1. L. Chaabane
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  2. L. Tei
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  3. L. Miragoli
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  4. L. Lattuada
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  5. M. von Wronski
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  8. S. Aime
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Corresponding author

Correspondence to S. Aime.

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Chaabane, L., Tei, L., Miragoli, L. et al. In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide. Mol Imaging Biol 17, 819–828 (2015). https://doi.org/10.1007/s11307-015-0846-4

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  • DOI: https://doi.org/10.1007/s11307-015-0846-4

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