Abstract 5279: Imaging of pancreatic cancer with activated cell penetrating peptide dendrimers

Abstract

Abstract We have recently described novel activatable cell penetrating peptides attached to dendrimers (ACPPDs) which can selectively label tumors for real-time imaging during surgery. The aim of this study was to evaluate the ability of Cy5-labeled ACPPDs to visualize primary tumors and their margins in an orthotopic mouse model of pancreatic cancer. BxPC-3 or BxPC-3-RFP-expressing human pancreatic cancer cells were injected into the pancreas of 6-week old athymic mice to establish the orthotopic mouse models. ACPPs were synthesized on an automated peptide synthesizer by using standard protocols for fluorenylmethoxycarbonyl solid-phase synthesis. Peptides were cleaved off the resin, purified by HPLC, and conjugated to a generation 5 PAMAM dendrimer. Cy5 labeling was performed directly on the dendrimer. Dendrimers were then capped completely with Peg4 NHS ester. Tumor-bearing mice were injected with 20 nmoles of ACPPDs via tail vein 48 hours prior to imaging. Mice were first imaged non-invasively using OV-100 (Olympus) or Maestro (CRI) small animal imaging systems. Mice then underwent laparotomy. Resection of the primary pancreatic tumor using fluorescence guidance was performed using a MVX-10 fluorescence-dissecting microscope (Olympus) customized to allow the surgeon to see white-light reflectance, fluorescence, or the two superimposed in real time. At the conclusion of the experiments, H&E staining was used to confirm the pathological diagnosis of cancer in the resected specimens. We found that in the orthotopic BxPC3 mouse model of pancreatic cancer, intravenous injection of ACPPD showed bright fluorescence labeling of tumors compared to surrounding normal tissue. Co-localization studies showed a good correlation between ACPPD uptake and RFP tumor expression. Tumor margins were more clearly delineated with fluorescence imaging using ACPPDs compared to with white light reflectance alone. Post resection, the tumor bed was examined and imaged for residual tumor. With fluorescence-guided resection, the tumor bed was free of residual tumor, which was confirmed histologically. In this study, we have shown that ACPPDs can accurately and effectively label primary pancreatic tumors in an orthotopic mouse model of pancreatic cancer. This technology has the potential to improve surgical outcomes in patients with pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5279. doi:10.1158/1538-7445.AM2011-5279