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.

项目概要 一些癌症患者的一线治疗是手术减瘤，其肿瘤可能较差 本地化导致长时间不完整的手术和重复就诊。我们的目标是为医生提供服务。 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，以及2）术后分子表达信息 改善口腔鳞状细胞癌 (OSCC) 的治疗决策。 开发我们新的多模态成像方法，因为它的肿瘤分界较差且易于访问 我们打算开发一种新型多峰纳米颗粒（NP）来服务。 作为我们的肿瘤靶向造影剂，这些新的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期间的指导，以识别分子表达和药物 这些多模式 NP 有可能为医生提供有效治疗的目标。 肿瘤的分子图谱具有更高的灵敏度和特异性，这是以前现有的单一图谱无法实现的 模式分子成像技术面临着开发新造影剂的持续努力。 我们的创新方法使用的染料已获得 FDA 批准，这是获得监管批准的主要问题。 批准用于食品、药品和化妆品的着色 颜色就在我们身边，但我们常常误认为是颜色。 我们好奇地了解了我们最喜欢的糖果、化妆品和服装中鲜艳色彩的来源。 考虑到这些“色彩缤纷”的有机染料不仅仅能提供美观，我们最近发现 事实上，它们具有许多有用的光学特性（例如吸光度、荧光、拉曼散射） 使它们成为成像应用的理想选择。我们建议将这些染料及其多模态成像集成起来。 功能融入纳米颗粒结构中，专门设计用于提供有用的成像对比度，使 我们将通过表征癌症来开始我们的研究。 这些新制造的纳米粒子的物理特性及其多模态成像能力。 利用多分子成像对其生物分布和外渗特性进行体内评估 然后我们将测试它们在细胞培养和人体组织中的肿瘤靶向效率。 通过化学缀合靶向配体主动靶向肿瘤和/或通过 我们将评估肿瘤靶向效率和手术的增强渗透性和保留效果。 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重新利用为多峰染料 成像探针可实现全新的、可临床翻译的范例。 这些多模式纳米颗粒可以改善癌症检测和定位，从而改善手术切除， 还协助设计最适合患者个体的治疗方案。