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

1403191/1402353 Anvari，Bahman/Kundra，Vikas标题：合作研究：卵巢癌成像和治疗的新范式意义：这是一份由加州大学滨江分校生物工程系博士Bahman Anvari和放射学和癌症系统成像系博士Vikas Kundra提交的合作申请，德克萨斯大学MD安德森癌症中心诊断成像部。研究人员建议使用一种新的光学纳米探针，由生物和有机材料组成，用于小鼠模型中卵巢肿瘤的成像和激光治疗。通过本研究获得的知识对开发集成成像系统具有更广泛的意义和重要性，该系统可能成为早期检测卵巢癌（一个重大的公共卫生问题）的常规护理标准的一部分。这种集成系统也可用于检测和去除目前在术前或手术时未被识别的卵巢肿瘤。这种能力是重要的，因为所有肿瘤结节的完全手术切除对患者的生存至关重要。拟议的研究还为教育推广提供了一个平台。这些活动将包括在UCR代表性不足的学生的参与，并提供多学科的培训机会，以获得生物光子学，纳米材料和纳米科学，以及肿瘤成像的技能。技术说明：研究人员的长期目标是开发一种新的模式，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）的成像方法，或通过手术期间的目视检查，通常无法检测到小的卵巢肿瘤结节（直径1 cm）。这种结节，如果没有被发现和去除，可能会导致复发和患者生存率低。目前的治疗方法，基于细胞减灭术，然后是标准的化疗药物不是很有效，主要是因为前者不完全切除所有肿瘤，而后者缺乏疗效。 作为第一步，研究人员有兴趣研究具有分子靶向，近红外（NIR）成像和光疗能力的光学纳米结构平台在植入卵巢肿瘤异种移植物的小鼠模型中的效用。该平台由NIR发色团吲哚花青绿色（ICG）组成，其被源自植物感染雀麦花叶病毒的衣壳蛋白的壳包封。该平台被称为光学病毒幽灵（OVGs）。壳的外表面将用针对人表皮生长因子受体-2（HER-2）的单克隆抗体功能化，HER-2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相关。该提案的具体目的是研究：（1）抗HER-2功能化的OVGs作为小鼠腹膜内卵巢肿瘤靶向递送平台的有效性;（2）小鼠异种移植肿瘤的图像引导光热破坏的有效性;（3）输卵管癌的概念验证NIR荧光成像。最后一个特定的目标是探索，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.