Abstract 4238: Multispectral optoacoustic tomography detects orthotopic pancreatic tumors in vivo using a nano-contrast agent

Abstract

Abstract There have been very modest developments in pancreatic cancer detection and treatment with mortality essentially remaining unchanged in the last four decades. The major challenge for both early detection and treatment of pancreatic tumors lies in overcoming various biological barriers, especially poor perfusion, insufficient contrast agents/drugs uptake by the tumor, and limitations of traditional imaging modalities. The combination of accurate real-time imaging with tumor-specific nano-contrast agents could mitigate these impediments. We constructed highly stable nano-contrast agents by encapsulating GNRs having aspect ratio 3:1 in PAA (1.5 ± 0.5 nm), and MS (6.25 ± 0.25 nm) shell, respectively and targeted to insulin growth factor 1 receptor (IGF1-R) positive pancreatic tumor cells via Syndecan-1 ligand. IGF1-R specific binding of Syndecan-MS GNRs and Syndecan-PAA-GNR was determined using in an IGF1-R negative cell line (MiaPaca-2) or a blocking antibody to IGF1-R in S2VP10L pancreatic cancer cells determined via flow cytometry. In vivo, mice bearing orthotopic pancreatic tumors were iv injected with 100 nM of Syndecan-MS GNRs and accumulation was determined four hours post injection via Multispectral Optoacoustic Tomography. Biodistribution was determined using a Region of Interest method. The cellular uptake of Syndecan-MS-GNRs significantly enhanced in the S2VP10L cells (503.4 counts) compared to MiaPaca-2 cells (64.1 counts), blocking agent (323.7counts) and untargeted MS GNRs (average 47 counts) revealing that Syndecan-MS-GNRs enhanced both tumor specificity and OA signals by binding with IGF1-R in S2VP10L cells. In vivo, Syndecan-MS-GNRs significantly accumulated in S2VP10L orthotopic pancreatic tumors (233.1 MSOT a.u.) with minimal accumulation in kidney(29.7 MSOT a.u.) and liver (31.4 MSOT a.u.). The Syndecan-MS-GNRs did not accumulate within the orthotopic MiaPaca-2 (IGF1-R negative) mouse model with the biodistribution of pancreas tumor (12.4 MSOT a.u.), kidney (114.3 MSOT a.u.), and liver (35.2 MSOT a.u.). Citation Format: Phillip Chuong, Matthew Zeiderman, William E. Grizzle, Lacey R. McNally. Multispectral optoacoustic tomography detects orthotopic pancreatic tumors in vivo using a nano-contrast agent. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4238.