Abstract 4196: Real-time single-walled nanotube (SWNT)-based imaging system improves tumor detection and survival in ovarian cancer animal model

Abstract

Abstract Residual tumor detection in advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of this disease. Optimal abdominal cytoreduction to reduce tumor to no evidence of macroscopic disease is the main endpoint of tumor debulking surgery, with demonstrated survival advantages, but the current clinically available imaging modalities have shown low tumor detection sensitivity of tumors smaller than 10 mm diameter. Instead, targeted molecule-based imaging systems offer higher detection rate and are likely to extend the aim of complete resection to the microscopic scale. We applied a custom designed imaging system to a preclinical ovarian cancer tumor model and observed higher microscopic tumor detection accuracy and survival advantage compared to non-image guided debulking surgery. A two component imaging system was developed. The contrast agent is an intra-peritoneal injectable nanomolecular probe, composed of a single walled carbon nanotube (SWNT) coupled with an engineered M13-bacteriophage carrying a modified peptide targeting secreted protein, acidic and rich in cysteine (SPARC), extracellular protein overexpressed in OC. The imaging device system is capable of detecting SWNT inherent fluorescence in near-infrared second window (NIR2) and of displaying real-time images to guide the intraoperative tumor debulking. In an orthotopic ovarian cancer animal model, the imaging system detected microscopic tumors in the millimeter and sub-millimeter scale resolution with a mean tumor diameter of 2.1 vs 3.6 mm (p< 0.01) compared to eye detected tumors. The imaging system demonstrated sensitivity of 97.2% and specificity of 69.7%, and a Receiver Operator Area under the Curve of 0.85 + 0.05. In a survival surgery animal model, the imaging guided resection surgery compared to non guided surgery showed a survival advantage for the experimental arm, with median survival time of 41.0 days vs 28.5 days, respectively (HR 0.22, 95% CI of ratio 0.04 to 1.08 Log Rank test: p: 0.063). The accuracy of the imaging system and its survival advantage are promising. The survival outcome improvement in this preclinical model supports the translation to first-in-human investigation. Moreover, the imaging system accuracy suggests further exploitation in targeted delivery therapies. Citation Format: Lorenzo Ceppi, YoungJeong Na, Neelkanth M. Bardhan, Andrew Siegel, Nandini Rajan, Angela M. Belcher, Michael J. Birrer. Real-time single-walled nanotube (SWNT)-based imaging system improves tumor detection and survival in ovarian cancer animal model. [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 4196.