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

1403191/1402353安瓦里，巴赫曼/昆德拉，维卡斯标题：合作研究：卵巢癌成像和治疗的新范式意义：这是由加州大学河滨分校生物工程系的巴赫曼·安瓦里博士和德克萨斯大学MD安德森癌症中心诊断成像系的维卡斯·昆德拉提交的合作申请。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测器，在小鼠模型中对卵巢肿瘤进行成像和基于激光的治疗。通过这项研究获得的知识对开发综合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发现的常规护理标准的一部分，卵巢癌是一个重大的公共卫生问题。这样的集成系统也可以用于检测和移除目前在手术前或手术中未被识别的卵巢肿瘤。这一能力是重要的，因为完全手术切除所有的肿瘤结节对患者的生存至关重要。拟议的研究还为教育宣传提供了一个平台。这类活动将包括UCR代表人数不足的学生参加，并提供一个多学科培训机会，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CT和磁共振(MR)或术中肉眼检查的成像方法往往不能发现卵巢肿瘤小结节(直径1 cm)。这种结节如果不被发现和切除，可能会导致复发和低患者存活率。目前的治疗方法，以细胞减灭术为主，辅以标准化疗药物治疗效果不是很好，主要原因是前者切除肿瘤不完全，后一种方法缺乏疗效。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)成像和光治疗能力的光学纳米结构平台在植入卵巢肿瘤异种移植瘤的小鼠模型中的应用。这个平台由近红外发色团吲哚青绿(ICG)组成，由侵染植物的雀麦花叶病毒衣壳蛋白包裹。该平台被称为光学病毒幽灵(OVG)。外壳的外表面将用抗人表皮生长因子受体-2(HER-2)的单抗进行功能化，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有关。该建议的具体目的是研究：(1)以抗HER-2为靶向递送平台的OVGs对小鼠腹膜内卵巢肿瘤的靶向递送作用；(2)图像导引下光热杀灭小鼠异种移植瘤的有效性；(3)近红外荧光成像技术对输卵管癌的靶向治疗作用。最后一个具体目标是探索，因为某些类型的卵巢癌可能发生于输卵管上皮；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.