Development of a peptidea??functionalized imaging nanoprobe for the targeting of (FXYD2)?3a as a highly specific biomarker of pancreatic beta cells

摘要

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 nona??invasively the BCM in diabetic patients. Our work describes a phage displaya??derived peptide (P88) that is highly specific to (FXYD2)?3a 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/mm3 in vitro after conjugation to ultraa??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 Capana??2 tumours that also express (FXYD2)?3a. A strong negative contrast was obtained subsequent to the injection of USPIOa??P88, but not in negative controls. On human histological sections, USPIOa??P88 seems to be specific to pancreatic beta cells, but not to duodenum, stomach or kidney tissues. USPIOa??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 USPIOa??P88 injection could provide important information for the future pancreatic BCM evaluation by MRI. Copyright ?? 2015 John Wiley & Sons, Ltd.