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2018-08-21 - Article/Dans un journal avec peer-review - Anglais - 16 page(s)

Demine Stéphane, Balhuizen Alexander, Debaille Vinciane, Joosten Lieke, Fereau Maïté, Chilla Satya Narayana Murthy, Millard Isabelle, Scharfmann Raphaël, Egrise Dominique, Goldman Serge, Marchetti Piero, Gotthardt Martin, Laurent Sophie , Burtea Carmen , Eizirik Decio, "Imaging of Human Insulin Secreting Cells with Gd-DOTA-P88, a Paramagnetic Contrast Agent Targeting the Beta Cell Biomarker FXYD2 gamma-a" in Molecules

  • Edition : Multidisciplinary Digital Publishing Institute (MDPI) (Switzerland)
  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Endocrinologie (DI3322), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Diabétologie (DI3373), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
  • 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)
Texte intégral :

Abstract(s) :

(Anglais) Non-invasive imaging and quantification of human beta cell mass remains a major challenge. We performed pre-clinical in vivo validation of a peptide previously discovered by our group, namely, P88 that targets a beta cell specific biomarker, FXYD2 gamma-a. We conjugated P88 with DOTA and then complexed it with GdCl3 to obtain the MRI (magnetic resonance imaging) contrast agent (CA) Gd-DOTA-P88. A scrambled peptide was used as a negative control CA, namely Gd-DOTA-Scramble. The CAs were injected in immunodeficient mice implanted with EndoC-beta-H1 cells, a human beta cell line that expresses FXYD2 a similarly to primary human beta cells. The xenograft-bearing mice were analyzed by MRI. At the end, the mice were euthanized and the CA biodistribution was evaluated on the excised tissues by measuring the Gd concentration with inductively coupled plasma mass spectrometry (ICP-MS). The MRI and biodistribution studies indicated that Gd-DOTA-P88 accumulates in EndoC-beta-H1 xenografts above the level observed in the background tissue, and that its uptake is significantly higher than that observed for Gd-DOTA-Scramble. In addition, the Gd-DOTA-P88 showed good xenograft-to-muscle and xenograft-to-liver uptake ratios, two potential sites of human islets transplantation. The CA shows good potential for future use to non-invasively image implanted human beta cells.

Identifiants :
  • DOI : 10.3390/molecules23092100

Mots-clés :
  • (Anglais) Type 2 diabetes
  • (Anglais) pancreatic beta cell
  • (Anglais) MRI
  • (Anglais) non-invasive imaging
  • (Anglais) peptide-based imaging
  • (Anglais) Type 1 diabetes
  • (Anglais) molecular imaging
  • (Anglais) paramagnetic contrast agent