Abstract 4320: Real-time monitoring of tumor-selective photosensitizer delivery in vivo using hyperspectral and endoscopic imaging technologies in an ovarian cancer model
Authors: Abu-Yousif Adnan O. , Spring Bryan Q. , Zheng Xiang , Rai Prakash R. , Hasan Tayyaba 
Published: February 2011

Abstract
Objective: Employ a combination of in vivo, cellular-resolution fluorescence microendoscopy (FME) and hyperspectral fluorescence small animal imaging to visualize and quantify photosensitizer delivery to tumor tissues in a murine model of disseminated ovarian cancer.
Rationale: Ovarian cancer is the fifth most lethal cancer among women in the United States, accounting for over 20,000 deaths annually. While most patients respond initially to systemic chemotherapy, they often develop resistance to standard platinum regimens. Photodynamic therapy (PDT) is a photochemistry based modality that our group has demonstrated is capable of reversing platinum resistance in human ovarian cancer cells and has shown promise in a murine model of ovarian cancer. An intrinsic advantage to PDT is that the photosensitizers (PS) emit fluorescence and can therefore be used as both an imaging agent and a light-activated therapeutic agent.
Effective drug delivery to malignant tissues continues to be a challenge when treating many diseases including ovarian cancer. While the liposomal formulation of benzoporphyrin derivative (BPD) preferentially accumulates in malignant tissues, our group has strived to improve tumor selective delivery of BPD, in order to minimize collateral damage when activating the photosensitizer in vivo, and to increase the BPD tumor payload to enhance tumor cell killing. In order to address these issues we have designed 1) a photoimmunoconjugate (PIC) generated by coupling the PS to the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody Cetuximab; and 2) a “nanocell” construct in which BPD is non-covalently trapped inside polymer nanoparticles, which are then encapsulated inside liposomes.
Methods: In the present study we have used PIC- and nanotechnology-based drug delivery platform to improve the tumor selectivity and the delivered payload efficiency of BPD. Real-time assessment of BPD delivery was assessed using two separate imaging modalities. We employed a minimally invasive FME to detect BPD in tumor and normal tissues in situ. Quantitative measurements of BPD fluorescent signals were taken using a hyperspectral small animal imaging system. The presence of tumor and PS localization was confirmed by histology and immunofluorescence.
Results and Conclusions: Quantitative imaging demonstrates enhanced BPD delivery by its encapsulation into a nanocell construct. Separately, our imaging results show enhanced tumor selectivity achieved by conjugating BPD to Cetuximab, in comparison to the traditional administration of BPD. The use of the advanced imaging platforms provides insight (and real-time feedback) regarding the localization and concentration of the photosensitizer in tumor tissues, which will lead to more effective treatment planning regimens for ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4320.