Abstract 62: Tumor targeted contrast agents for pancreatic adenocarcinoma

Abstract Purpose: Pancreatic cancer has a low relative survival rate of only 12.8%, with surgical resection being an option for just 20% of patients. Achieving R0 resection is vital, as it forms the cornerstone of curative treatment strategies. pH low insertion peptides (pHLIPs), a novel class of targeted imaging agents, are being developed for use with multispectral optoacoustic imaging (MSOT) for potential clinical or intraoperative applications. However, existing pHLIPs have limitations in dynamic range and solubility. To address these issues, a new pHLIP variant, V7Phe, was designed to enhance both solubility and dynamic range for identifying the acidic tumor microenvironment in pancreatic cancer. Methods: V7 and V7F peptides were synthesized using microwave chemistry, then removed from resin, lyophilized, and rehydrated. Conjugation with HiLyte 750 dye via maleimide chemistry was confirmed through spectroscopy. Pancreatic cancer cell lines S2VP10 and S2013 were treated with V7-750 and V7F-750 at pH 7.4 and pH 6.6. Probe uptake was assessed using near-infrared fluorescence imaging. Results: V7F-750 demonstrated a significantly higher signal in vitro than V7-750 at both pH 7.4 and pH 6.6 (p<0.01). V7F-750 also exhibited greater signal in more acidic conditions (p<0.01). Although solubility was moderately improved, V7F-750 did not show an enhanced dynamic range compared to V7-750, with the ratio of signal at pH 6.6 to 7.4 being 1.19 for V7F-750 versus 1.39 for V7-750 (p=0.21) across both cell lines. Conclusion: V7F-750 effectively targets the acidic tumor microenvironment, demonstrating improvements in peptide solubility Citation Format: Sylvana Knapp, Ryan Bynum, Molly McNally, William E. Grizzle, Lacey R. McNally. Tumor targeted contrast agents for pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 62.