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

L. Chaabane, L. Tei, L. Miragoli, L. Lattuada, M. von Wronski, F. Uggeri, V. Lorusso, S. Aime

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)819-828
Number of pages10
JournalMolecular Imaging and Biology
Volume17
Issue number6
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • Fibrin
  • Molecular imaging
  • MRI
  • Targeted contrast agent
  • Tumor model

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

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