L Chaabane1,2, L Tei3, L Miragoli2, L Lattuada2, M von Wronski4, F Uggeri2, V Lorusso5, S Aime6. 1. Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. 2. CRB Bracco Imaging S.p.A, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. 3. Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", Viale T. Michel 11, 15121, Alessandria, Italy. 4. Bracco Research SA, Route de la Galaise, 31, 1228, Plan-les-Ouates, Geneva, Switzerland. 5. Ephoran Multi Imaging Solutions, Bioindustry Park Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. 6. 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.
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.
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.
Entities:
Keywords:
Fibrin; MRI; Molecular imaging; Targeted contrast agent; Tumor model
Authors: Elmar Spuentrup; Rene M Botnar; Andrea J Wiethoff; Tareq Ibrahim; Sebastian Kelle; Marcus Katoh; Murat Ozgun; Eike Nagel; Josef Vymazal; Phil B Graham; Rolf W Günther; David Maintz Journal: Eur Radiol Date: 2008-04-19 Impact factor: 5.315
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