Development of a peptide-functionalized imaging nanoprobe for the targeting of (FXYD2)γa as a highly specific biomarker of pancreatic beta cells.
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.
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Carmen
C
Burtea
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Sophie
S
Laurent
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Deborah
D
Crombez
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Sébastien
S
Delcambre
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Corine
C
Sermeus
Center for Diabetes Research, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
Isabelle
I
Millard
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.|DIAPath, Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, 6041, Gosselies, Belgium.
Sandrine
S
Rorive
Center for Diabetes Research, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
Daisy
D
Flamez
Eurogentec S.A., Liège Science Park, Rue du Bois Saint-Jean 5, B-4102, Seraing, Belgium.
Marie-Claire
MC
Beckers
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.|DIAPath, Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, 6041, Gosselies, Belgium.
Isabelle
I
Salmon
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.
Luce
L
Vander Elst
Center for Diabetes Research, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
Decio L
DL
Eizirik
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000, Mons, Belgium.|Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, 6041, Gosselies, Belgium.
Robert N
RN
Muller
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D015415:Biomarkers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D010455:Peptides; C000499:ferric oxide; C498816:Fxyd2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
beta cell biomarker; beta cell mass; functionalized iron oxide nanoparticles; molecular imaging; pancreas; peptide