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Contrast Media Mol Imaging. 2015 Sep-Oct;10(5):398-412. doi: 10.1002/cmmi.1641. Epub 2015 Apr 30.

Development of a peptide-functionalized imaging nanoprobe for the targeting of (FXYD2)γa as a highly specific biomarker of pancreatic beta cells.

Author information

1
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
2
Center for Diabetes Research, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
3
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
4
DIAPath, Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, 6041, Gosselies, Belgium.
5
Eurogentec S.A., Liège Science Park, Rue du Bois Saint-Jean 5, B-4102, Seraing, Belgium.
6
Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, 6041, Gosselies, Belgium.

Abstract

Diabetes is characterized by a progressive decline of the pancreatic beta cell mass (BCM), which is responsible for insufficient insulin secretion and hyperglycaemia. There are currently no reliable methods to measure non-invasively the BCM in diabetic patients. Our work describes a phage display-derived peptide (P88) that is highly specific to (FXYD2)γa expressed by human beta cells and is proposed as a molecular vector for the development of functionalized imaging probes. P88 does not bind to the exocrine pancreas and is able to detect down to ~156 human pancreatic islets/mm(3) in vitro after conjugation to ultra-small particles of iron oxide (USPIO), as proven by the R2 measured on MR images. For in vivo evaluation, MRI studies were carried out on nude mice bearing Capan-2 tumours that also express (FXYD2)γa. A strong negative contrast was obtained subsequent to the injection of USPIO-P88, but not in negative controls. On human histological sections, USPIO-P88 seems to be specific to pancreatic beta cells, but not to duodenum, stomach or kidney tissues. USPIO-P88 thus represents a novel and promising tool for monitoring pancreatic BCM in diabetic patients. The quantitative correlation between BCM and R2 remains to be demonstrated in vivo, but the T2 mapping and the black pixel estimation after USPIO-P88 injection could provide important information for the future pancreatic BCM evaluation by MRI.

KEYWORDS:

beta cell biomarker; beta cell mass; functionalized iron oxide nanoparticles; molecular imaging; pancreas; peptide

PMID:
25930968
DOI:
10.1002/cmmi.1641
[Indexed for MEDLINE]

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