Development of a peptide‐functionalized imaging nanoprobe for the targeting of (FXYD2)γa as a highly specific biomarker of pancreatic beta cells. (30th April 2015)

• Record Type: Journal Article
• Authors: Burtea, Carmen; Laurent, Sophie; Crombez, Deborah; Delcambre, Sébastien; Sermeus, Corine; Millard, Isabelle; Rorive, Sandrine; Flamez, Daisy; Beckers, Marie‐Claire; Salmon, Isabelle; Vander Elst, Luce; Eizirik, Decio L.; Muller, Robert N.
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 5(2015:Sep./Oct.)
• Page Start: 398
• Page End: 412
• Publication Date: 2015-04-30
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1641
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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<sup>3</sup><italic>in vitro</italic> after conjugation to ultra‐small particles of iron oxide (USPIO), as proven by the <italic>R</italic><sub>2</sub> measured on MR images. For <italic>in vivo</italic> 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 <italic>R</italic><sub>2</sub> remains to be demonstrated <italic>in vivo</italic>, but the <italic>T</italic><sub>2</sub> mapping and the black pixel estimation after USPIO–P88 injection could provide important information for the future pancreatic BCM evaluation by MRI. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>