Collaborative Research: A new paradigm for ovarian cancer imaging and therapy

1403191/1402353Anvari, Bahman/Kundra， vikas标题：合作研究：卵巢癌成像和治疗的新范例意义：这是由加州大学河滨分校生物工程系Bahman Anvari博士和德克萨斯大学MD安德森癌症中心诊断成像部放射学和癌症系统成像系Vikas Kundra博士共同提交的一份合作申请。研究人员建议使用一种由生物和有机材料组成的新型光学纳米探针，用于小鼠模型卵巢肿瘤的成像和激光治疗。通过本研究获得的知识对于开发集成成像系统具有更广泛的意义和重要性，该系统可能成为卵巢癌早期检测的常规标准护理的一部分，这是一个重大的公共卫生问题。这种集成系统还可用于检测和切除目前在手术前或手术中未发现的卵巢肿瘤。这种能力是重要的，因为手术完全切除所有肿瘤结节对患者的生存至关重要。拟议的研究也为教育推广提供了一个平台。这些活动将包括UCR代表性不足的学生的参与，并提供多学科培训机会，以获得生物光子学，纳米材料和纳米科学以及肿瘤成像方面的技能。技术说明：研究人员的长期目标是开发一种新的范例，通过改进成像和治疗方法，结合术中或腹腔镜手术，减轻卵巢癌的负担。目前基于术前计算机断层扫描（CT）和磁共振（MR）或术中目视检查的成像方法通常无法检测到卵巢小肿瘤结节（直径1厘米）。这样的结节，如果不及时发现和切除，可能会导致复发和低生存率。目前的治疗方法，在细胞减少手术的基础上，再加上标准的化疗药物，效果不是很好，主要是因为前者不能完全切除所有的肿瘤，而后者缺乏疗效。作为第一步，研究人员感兴趣的是研究具有分子靶向、近红外（NIR）成像和光疗能力的光学纳米结构平台在移植卵巢肿瘤的小鼠模型中的应用。该平台由近红外发色团吲哚菁绿（ICG）组成，由植物侵染雀梅花叶病毒衣壳蛋白衍生的外壳包裹。该平台被称为光学病毒幽灵（ovg）。壳的外表面将被单克隆抗体功能化，以对抗人表皮生长因子受体-2 (HER-2)，这是OVGs的分子靶点，其在卵巢癌细胞上的过度表达与癌症进展和死亡的风险增加有关。本研究的具体目的是研究：(1)抗her -2功能化的OVGs作为小鼠腹腔内卵巢肿瘤靶向递送平台的有效性；(2)图像引导光热破坏小鼠异种移植肿瘤的有效性；(3)输卵管癌近红外荧光成像的概念验证。最后一个具体目的是探讨，因为某些类型的卵巢癌可能来自输卵管上皮；因此，卵巢癌的早期阶段有可能被识别和治疗。

1403191/1402353Anvari, Bahman/Kundra, VikasTitle: Collaborative research: a new paradigm for ovarian cancer imaging and therapySignificance: 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 system that can potentially become part of routine standard of care for early detection of ovarian cancer, a significant public health problem. Such an integrated system may also be used 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. Technical Explanation: 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.