A New Multimodal Molecular Imaging Approach to Guide Intra-Operative Tumor Resection and Post-Operative Treatment Planning

一种新的多模态分子成像方法来指导术中肿瘤切除和术后治疗计划

• 批准号: 10578468
• 负责人: Cristina L. Zavaleta
• 金额: $ 62.76万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578468
• 关键词: Acceleration; Affinity; Antibody Avidity; Area; Binding; Biodistribution; Biological Markers; CTLA4 gene; Cancer Detection; Cancer Patient; Cancer cell line; Cancerous; Candy; Cell Culture Techniques; Cells; Characteristics; Charge; Chemicals; Circulation; Clinical; Clothing; Color; Contrast Media; Cosmetics; Curiosities; Decision Making; Drug Targeting; Dyes; Ensure; Epidermal Growth Factor Receptor; Esthetics; Excision; Extravasation; FDA approved; Failure; Flow Cytometry; Fluorescence; Food; Goals; Gold; Growth; Half-Life; Health Care Costs; Hispanic; Household; Human; Image; Image-Guided Surgery; Imaging Device; Imaging technology; Immunotherapy; In Vitro; Ligands; Location; Malignant Neoplasms; Maps; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Monoclonal Antibodies; Morbidity - disease rate; Multimodal Imaging; Mus; Nanosphere; Operative Surgical Procedures; Optics; Outcome; Paint; Patient-Focused Outcomes; Patients; Performance; Permeability; Pharmaceutical Preparations; Physicians; Postoperative Period; Prediction of Response to Therapy; Property; Protein Analysis; Proteins; Public Health; Publishing; Repeat Surgery; Research; Resected; Resolution; Sensitivity and Specificity; Silicon Dioxide; Source; Surface; Surgeon; Testing; Therapeutic; Time; Toxic effect; Translating; Treatment Protocols; Tumor Debulking; Tumor Tissue; Visit; Xenograft Model; antibody conjugate; cancer imaging; cancer type; career development; chemical conjugate; chemical property; clinical translation; contrast imaging; cost effective; design; effective therapy; fabrication; fluorescence imaging; human tissue; image guided; imaging approach; imaging capabilities; imaging modality; imaging potential; imaging probe; imaging properties; improved; in vivo; in vivo evaluation; individual patient; innovation; molecular imaging; mouth squamous cell carcinoma; multimodality; multiplexed imaging; nano; nanoparticle; novel; optical imaging; overexpression; patient stratification; personalized medicine; pre-clinical; predicting response; professor; programmed cell death protein 1; specific biomarkers; targeted biomarker; targeted treatment; tenure track; therapy design; therapy outcome; treatment planning; treatment response; treatment stratification; tumor; tumor growth

Project Summary The first line of treatment for several cancer patients is surgical debulking which can suffer from poor tumor localization resulting in lengthy incomplete surgeries and repeat visits. Our objective is to provide physicians with an entirely new multimodal molecular imaging strategy that has the potential to offer 1) intra-operative surgical guidance to ensure complete resection of the tumor, and 2) post-operative molecular expression information to improve therapeutic decision-making. Oral squamous cell carcinoma (OSCC) is an ideal cancer on which to develop our new multimodal imaging approach as it suffers from poor tumor demarcation and is easy to access with optical imaging tools. We intend to develop an entirely new class of multimodal nanoparticles (NPs) to serve as our tumor targeting contrast agents. These new NPs are intended to provide real-time fluorescence image guidance during tumor resection and Raman multiplexed imaging to identify molecular expression and drug target availability for effective therapy. These multimodal NPs have the potential to provide physicians with a molecular map of the tumor with improved sensitivity and specificity not previously achievable with existing single mode molecular imaging technologies. Ongoing attempts toward developing new contrast agents have faced major problems in gaining regulatory approval. Our innovative approach utilizes the dyes that are already FDA approved for the coloring of our foods, drugs and cosmetics. Color is all around us, however, we often take for granted the sources of the vibrant colors we enjoy in our favorite candy, cosmetics and clothing. After curiously considering that these “colorful” organic dyes could offer more than just aesthetics, we recently discovered that they in fact have a multitude of useful optical properties (e.g. absorbance, fluorescence, Raman scattering) that make them ideal for imaging applications. We propose to integrate these dyes and their multimodal imaging capabilities into a nanoparticle construct specially designed to provide useful imaging contrast that enables improved cancer detection, localization and molecular profiling. We will begin our study by characterizing the physical characteristics of these newly fabricated NPs and their multimodal imaging capabilities. This will include in-vivo evaluation of their biodistribution and extravasation properties by utilizing multiple molecular imaging tools. We will then test their tumor targeting efficiency in cell culture and on human tissue. Our nanoparticles will actively target tumors through chemically conjugated targeting ligands and/or passively target the tumor through the enhanced permeability and retention effect. We will assess the tumor targeting efficiency and surgical navigation potential of our newly developed NPs with pre-existing preclinical and clinical molecular imaging tools. These studies will enable the repurposing of these aesthetically pleasing household organic dyes as multimodal imaging probes to enable an entirely new, and clinically translatable, paradigm. The images generated from these multimodal nanoparticles could improve cancer detection and localization for improved surgical resection, but also aid clinicians in the design of treatment protocols which are most suitable for the individual patient.

项目摘要 一线治疗的几个癌症患者是手术减瘤，可遭受穷人的肿瘤 本地化导致冗长的不完整手术和重复访问。我们的目标是为医生提供 一种全新的多模式分子成像策略，有可能提供1）术中手术 指导以确保肿瘤的完全切除，和2）术后分子表达信息， 改善治疗决策。口腔鳞状细胞癌（OSCC）是一种理想的癌症， 开发我们新的多模式成像方法，因为它的肿瘤分界差，易于访问 光学成像工具。我们打算开发一种全新的多峰纳米颗粒（NPs）， 作为我们的肿瘤靶向造影剂这些新纳米粒子旨在提供实时荧光图像 肿瘤切除和拉曼多重成像过程中的指导，以识别分子表达和药物 有效治疗的目标可用性。这些多模态纳米颗粒有可能为医生提供一个 肿瘤的分子图谱，具有以前用现有的单一方法无法实现的提高的灵敏度和特异性 模式分子成像技术。正在进行的开发新造影剂的尝试面临着 获得监管部门批准的主要问题。我们的创新方法利用了FDA已经批准的染料， 用于食品药品和化妆品的着色色彩就在我们身边，然而，我们常常把它当作 我们喜爱的糖果、化妆品和服装中的鲜艳色彩来源于此。在好奇地 考虑到这些“彩色”有机染料可以提供的不仅仅是美学，我们最近发现， 它们实际上具有多种有用的光学性质（例如，吸光度、荧光、拉曼散射）， 使其成为成像应用的理想选择。我们建议整合这些染料和他们的多模态成像 将功能融入专门设计的纳米颗粒结构中，以提供有用的成像对比度，从而实现 改进癌症检测、定位和分子分析。我们将开始我们的研究， 这些新制造的NP的物理特性及其多模态成像能力。这将包括 通过利用多分子成像对其生物分布和外渗性质的体内评价 工具.然后，我们将在细胞培养和人体组织中测试它们的肿瘤靶向效率。我们的纳米粒子 通过化学缀合的靶向配体主动靶向肿瘤和/或通过化学缀合的靶向配体被动靶向肿瘤， 增强的渗透性和保留效果。我们将评估肿瘤靶向效率和外科手术 我们新开发的纳米粒子与现有的临床前和临床分子成像工具的导航潜力。 这些研究将使这些美观的家用有机染料的再利用成为多模态 成像探针，以实现一个全新的，临床上可翻译的范例。生成的图像 这些多模态纳米颗粒可以改善癌症检测和定位以改善手术切除， 而且还帮助临床医生设计最适合于个体患者的治疗方案。