title: In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.|CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy.
authors: L
authors: L
authors: Chaabane
authors: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", Viale T. Michel 11, 15121, Alessandria, Italy.
authors: L
authors: L
authors: Tei
authors: CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy.
authors: L
authors: L
authors: Miragoli
authors: CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy.
authors: L
authors: L
authors: Lattuada
authors: Bracco Research SA, Route de la Galaise, 31, 1228, Plan-les-Ouates, Geneva, Switzerland.
authors: M
authors: M
authors: von Wronski
authors: CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy.
authors: F
authors: F
authors: Uggeri
authors: Ephoran Multi Imaging Solutions, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy.
authors: V
authors: V
authors: Lorusso
authors: Dipartimento di Biotecnologie Molecolari e Scienze per la Salute and Molecular Imaging Center, Università di Torino, Via Nizza 52, 10125, Torino, Italy. silvio.aime@unito.it.
authors: S
authors: S
authors: Aime
mesh_terms: D000818:Animals; D005337:Fibrin / Q000378:metabolism*; D005682:Gadolinium / Q000008:administration & dosage*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000008:administration & dosage*
chemical_list: D010455:Peptides; D005337:Fibrin; D005682:Gadolinium
keywords: Fibrin; MRI; Molecular imaging; Targeted contrast agent; Tumor model