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

作者：Burtea Carmen^*; Laurent Sophie; Crombez Deborah; Delcambre Sebastien; Sermeus Corine; Millard Isabelle; Rorive Sandrine; Flamez Daisy; Beckers Marie Claire; Salmon Isabelle; Vander Elst Luce; Eizirik Decio L; Muller Robert N

来源：Contrast Media and Molecular Imaging, 2015, 10(5): 398-412.

DOI：10.1002/cmmi.1641

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

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)gamma a 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 similar to 156 human pancreatic islets/mm(3)in vitro after conjugation to ultra-small particles of iron oxide (USPIO), as proven by the R-2 measured on MR images. For in vivo evaluation, MRI studies were carried out on nude mice bearing Capan-2 tumours that also express (FXYD2)gamma a. 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 R-2 remains to be demonstrated in vivo, but the T-2 mapping and the black pixel estimation after USPIO-P88 injection could provide important information for the future pancreatic BCM evaluation by MRI.

• 出版日期2015-10