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
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 Diabetes Research, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
Contrast Media Mol Imaging. 2015 Sep-Oct;10(5):398-412. doi: 10.1002/cmmi.1641. Epub 2015 Apr 30.
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.
糖尿病的特征是胰腺β细胞量（BCM）逐渐减少，这导致胰岛素分泌不足和高血糖。目前尚无可靠的方法可对糖尿病患者的BCM进行无创测量。我们的研究描述了一种源自噬菌体展示的肽（P88），它对人β细胞表达的（FXYD2）γa具有高度特异性，并被提议作为开发功能化成像探针的分子载体。P88不与外分泌胰腺结合，与超小氧化铁颗粒（USPIO）偶联后，在体外能够检测低至约156个人类胰岛/mm³，这在磁共振图像上测得的R2得到了证实。为了进行体内评估，对携带也表达（FXYD2）γa的Capan - 2肿瘤的裸鼠进行了MRI研究。注射USPIO - P88后获得了强烈的负性对比，但在阴性对照中未获得。在人类组织切片上，USPIO - P88似乎对胰腺β细胞具有特异性，但对十二指肠、胃或肾脏组织无特异性。因此，USPIO - P88是监测糖尿病患者胰腺BCM的一种新颖且有前景工具。BCM与R2之间的定量相关性仍有待在体内得到证实，但注射USPIO - P88后的T2映射和黑色像素估计可为未来通过MRI评估胰腺BCM提供重要信息。
