Abstract LB-509: Early detection of pancreatic cancer in transgenic mice with ultrasonic molecular imaging and VEGFR2-targeted microbubbles

Abstract

Abstract Pancreatic cancer is a lethal disease largely due to presence of advanced and inoperable disease at the time of diagnosis. Evidence from current screening programs for high-risk individuals suggests that aggressive detection at operable stages could dramatically improve prognosis; however, current radiological imaging screen methods are not standardized and rely on solid mass recognition from anatomical/morphological imaging strategies. Incorporation of a molecular imaging strategy can provide a highly reliable and cancer-specific diagnosis, as well as, improved delineation of tumor boundaries for therapeutic and surgical guidance. Molecular ultrasound imaging is accomplished by conjugating targeting molecules (peptides/antibodies) to the surface of gas-filled microbubble contrast agents (1-4 μm diameter), and these contrast agents bind to markers overexpressed on disease-associated endothelium. In this study, we investigated the ability to detect small pancreatic cancers with contrast microbubbles targeted to vascular endothelial growth factor receptor type 2 (VEGFR2) and small animal transabdominal ultrasound (US) imaging in a transgenic mouse model of pancreatic cancer (Pdx1-Cre; KRasV12G; Ink4a-/-; PC mice). Small tumors ranging from 0.8 mm to 3.0 mm in diameter (mean: 1.7 ± 0.6 mm) could be detected with high-resolution B-mode US imaging, and showed 7.8-fold higher (P < 0.001) VEGFR2-targeted molecular US signal (mean signal intensity: 6.5 ± 8.4 arbitrary units; n=32 tumors) in PC mice compared with normal pancreas in wildtype mice (mean signal intensity: 0.8 ± 0.6 arbitrary units; n=14 mice). Small pancreatic tumors showed 3-fold higher VEGFR2-targeted US signal (mean signal intensity: 10.5 ± 9.4 arbitrary units) compared with US signal measured with non-targeted microbubbles (mean signal intensity: 3.6 ± 1.8 arbitrary units), indicating high specificity for VEGFR2. Ex vivo histological (H&E) analysis and immunostaining of VEGFR2 confirmed millimeter-sized tumors in the pancreas and VEGFR2 expression in PC mice (VEGFR2-positive tumors); in contrast, pancreas tissue from normal, wildtype mice was VEGFR2-negative. Taken together, these studies indicate that VEGFR2-targeted US imaging can detect small pancreatic cancers that are not normally recognized with conventional anatomical imaging, and may be highly useful for establishing a standardized pancreatic cancer screening/monitoring method for high-risk patients. Supported by the Canary Foundation, and NIH/NCI grants R21 CA139279 and Fellowship R25 CA11868. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-509. doi:1538-7445.AM2012-LB-509