A novel plectin/integrin-targeted bispecific molecular probe for magnetic resonance/near-infrared imaging of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies with poor patient outcomes often resulting from delayed diagnosis. Therefore, early diagnosis can lead to a better prognosis and improved outcomes. In this study, we have developed a novel conjugate complex of plectin/integrin-targeted bispecific molecular probe, termed Gd-Cy7-PTP/RGD, to be used for magnetic resonance/near-infrared imaging (MRI/NIRF) of pancreatic cancer in vivo. This bispecific molecular probe comprises four parts: Gd(III) for MRI, cyanine 7 (Cy7) for NIRF, the peptide PTP for binding to plectin-1 specifically overexpressed on the surface of PDAC cells, and the peptide RGD for targeting integrin widely expressed on pancreatic duct epithelial cells and angiogenesis. Remarkably, the combination of PTP and RGD greatly increased the targeting efficiency in vitro and in vivo compared to that of either single peptide. Moreover, such bispecific molecular probes target pancreatic neoplasms and angiogenesis simultaneously, producing a "multi-level" targeting effect confirmed by immunofluorescence testing in vitro and in vivo. Under the guidance of MRI/NIRF dual-modality imaging, NIRF-guided delineation of surgical margins during operations was successfully achieved in orthotopic pancreatic cancer. This study promotes further exploration of bispecific molecular probes for clinical application.