This is a collaborative application submitted by Bahman Anvari, PhD in the Department of Bioengineering at University of California, Riverside, and Vikas Kundra, MD, PhD in the Departments of Radiology and Cancer Systems Imaging, Division of Diagnostic Imaging at The University of Texas MD Anderson Cancer Center. The investigators propose the use of a new optical nano-probe, composed of biological and organic materials, for imaging and laser-based treatment of ovarian tumors in a mouse model. The knowledge gained through this study has broader significance and importance towards the development of an integrated imaging and phototherapeutic laparoscopic system that can potentially become part of routine standard of care for early detection of ovarian cnacer, a significant publich health problem. Such an integrated system may also be used intraoperatively to detect, and remove ovarian tumors that are currently not identified pre-surgery or at surgery. This capability is significant since the complete surgical removal of all tumor nodules is crucial towards patient survival. The proposed research also provides a platform for educational outreach. Such activities will include participation of under-represented students at UCR, and provide a multi-disciplinary training opportunity to acquire skills in biophotonics, nanomaterials and nanoscience, and oncologic imaging.
The long-term goals of the investigators are to develop a new paradigm that would reduce the burden of ovarian cancer by improved imaging and treatment methods in conjunction with intraoperative or laparoscopy procedures. Current imaging methods based on pre-operative computed tomography (CT) and magnetic resonance (MR), or by visual inspection during surgery, are frequently not capable of detecting small ovarian tumor nodules (diameter < 1 cm). Such nodules, if not detected and removed, can result in recurrence and low patient survival. Current treatment approach, based on cytoreductive surgery followed by standard chemotherapeutic agents are not very effective, mostly because of the incomplete resection of all tumors by the former, and lack of efficacy of the latter method. As the first steps, the investigators are interested in studying the utility of an optical nano-structured platform with molecular targeting, near infrared (NIR) imaging, and phototherapeutic capabilities in mice models implanted with ovarian tumor xenografts. This platform is comprised of the NIR chromophore, indocyanine green (ICG), encapsulated by a shell derived from the capsid proteins of the plant-infecting brome mosaic virus. The platform is referred to as optical viral ghosts (OVGs). The outer surface of the shell will be functionalized with a monoclonal antibody against the human epidermal growth factor receptor-2 (HER-2), the molecular target of OVGs, whose over-expression on ovarian cancer cells is associated with increased risk of cancer progression and death. The specific aims of this proposal are to investigate: (1) the effectiveness of OVGs functionalized with anti-HER-2 as a targeted delivery platform to intraperitoneal ovarian tumors in mice; (2) the effectiveness of image-guided photothermal destruction of xenografted tumors in mice; (3) and proof-of-concept NIR fluorescence imaging of fallopian tube carcinomas. The last specific aim is explored since some types of ovarian cancers may arise from the fallopian tube epithelium; thus early stages of ovarian cancer could potentially be identified, and treated.
