DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2017-03-16 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Fanfone Deborah , Paternoster Quentin, Stanicki Dimitri , Fossepre Mathieu , Surin Mathieu , Rorive Sandrine, Vander Elst Luce , Laurent Sophie , Muller Robert , Saussez Sven , Burtea Carmen , "Imaging of papillary thyroid cancer using peptide vectorized iron oxide nanoparticles targeted to galectin-1" in 3rd Belgium Molecular Imaging Congress , Bruxelles, Belgique, 2017

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biologie moléculaire (DI3111), Imagerie médicale, radiologie, tomographie (DI3243), Cancérologie (DI3349), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie des matériaux nouveaux (S817), Chimie générale, organique et biomédicale (M108), Anatomie et Biologie cellulaire (M112)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)

Abstract(s) :

(Anglais) Introduction : These last decades, the incidence of thyroid cancer (TC) has increased. The diagnostic challenge consists in the distinction of benign and malign nodules. Despite its high incidence, 90% of surgeries (non-cost effective and painful) performed on nodules reveal a benign phenotype (1). We propose to develop a new and non-invasive diagnosis approach by molecular MRI of papillary TC (PTC) by targeting galectin-1 (gal-1) with peptide functionalized Ultra-Small Particles of Iron Oxide (USPIO). Overexpressed in several human cancers including thyroid, gal-1 is implied in tumour progression and in metastasis development (2). Methods The phage display technique was used to identify phage clones expressing gal-1-targeted peptides. After the selection of phage clones with high affinity towards gal-1, corresponding peptides were synthesized. Immunohistochemistry studies on human TC sections were performed to confirm the peptides’ affinity and immunofluorescence assays were made on TPC-1 cells (derived from PTC) to attest their co-localization with gal-1. The interaction of peptides with gal-1 was also approached with docking studies. The selected peptides were conjugated to USPIO. Their binding and co-localization with gal-1 were demonstrated with Perls’-DAB and immunofluorescence assays on TPC-1 cells. The cytotoxicity of peptides and vectorized nanoparticles was evaluated by MTT. Xenografts of thyroid tumour were developed in athymic mice and the targeting efficacy of USPIO-P1 and USPIO-P7 was evaluated by MRI. Results : Selected peptides (P1, P7) bind to thyroid tumour biopsies and co-localize with gal-1 in TPC-1 cells. The same results were obtained for USPIO-P1 and USPIO-P7 on TPC-1 cells. Moreover, they have shown no toxicity on hepatocytes. After 24 hours of incubation, P1 and P7 (500 nM) reduced the TPC-1 cells viability, as determined by MTT assay. This decrease of TPC-1 viability is not due to apoptosis phenomenon but to the reduced cell adhesion to the gal-1. P1 and P7 would prevent cell adhesion by interacting with gal-1 in the carbohydrate recognition domain based on the docking studies, suggesting a therapeutic potential. A slight darkening of the tumor has been observed on MRI images after injection of gal-1-targeted USPIO. Conclusions : USPIO-P1 and USPIO-P7 seem to be promising targeting agents against gal-1 for the PTC diagnosis by MRI. After completing biodistribution and pharmacokinetics studies, the vectorized contrast agents will be assessed on a significant number of TPC-1 xenografted mice. Peptides could significantly block the tumor cell adhesion to gal-1, suggesting an anti-metastatic effect. References / Aknowledgments: (1) F. Pacini et al., Annals of Oncology, 2010, 21, v214–v219 (2) Banh et al., Cancer Research, 2011, 71, 4423–4431 This work is supported by a Télévie-F.N.R.S. and an ARC grant. The biopsies were kindly provided by Professor I. Salmon and her team (ULB, Erasme Hospital).