Investigation of nanobubble nucleation by radiation therapy

放射治疗纳米气泡成核的研究

• 批准号: 10642367
• 负责人: Guillem Pratx
• 金额: $ 19.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642367
• 关键词: 3-Dimensional; Acoustics; Alpha Particles; Basic Science; Biological; Biological Assay; Biophysical Process; Cancer Patient; Caring; Cells; Clinical; Combined Modality Therapy; Cosmic Radiation; Darkness; Diagnostic; Dose; Dose Limiting; Exposure to; Focused Ultrasound; Focused Ultrasound Therapy; Gases; Hour; Human; In Vitro; Incidence; Investigation; Ionizing radiation; Kinetics; Lead; Liquid substance; Malignant Neoplasms; Measurement; Measures; Mechanics; Medicine; Membrane; Modality; Modeling; Neutrons; Normal tissue morphology; Optical Methods; Organ; Organelles; Organism; Outcome; Patients; Predisposition; Property; Radiation; Radiation Dose Unit; Radiation therapy; Reactive Oxygen Species; Resistance; Risk; Sampling; Scanning; Scheme; Seminal; Temperature; Therapeutic; Tissues; Toxic effect; Translations; Treatment Efficacy; Tumor Volume; Ultrasonics; Ultrasonography; Water; cell killing; clinical practice; design; experimental study; improved; in vivo; in vivo Model; innovation; ionization; irradiation; microscopic imaging; millimeter; nanobubble; nanosized; neoplastic cell; novel; particle; physical property; prevent; radioresistant; response; treatment planning; treatment strategy; tumor; ultrasound

Abstract This project investigates a little-known physical property of ionizing radiation, which has the potential to increase the therapeutic ratio of radiation therapy (RT). Several decades ago, it was observed that ionizing radiation could nucleate gas nanobubbles (NBs) in water and other liquids. Seminal experiments revealed the presence of NB in irradiated water, which manifested as a decrease in the ultrasound power required to achieve acoustic cavitation. These results raise a crucial yet unanswered question: Does ionizing radiation nucleate NBs in vivo, inside irradiated tissues? Radiation is widely used in medicine. The premise that NBs may be nucleated in patients during diagnostic scans or radiation therapy is significant because NBs could induce biological effects. In addition, their presence in the tissues may lower the threshold for acoustic cavitation, which suggest a novel mechanism for increasing the efficacy of radiation therapy. The first Aim of this project is to gather rigorous and comprehensive evidence of NB nucleation in irradiated cells in vitro. Sensitive assays, including darkfield microscopy and ultrasound imaging, will be used to detect NBs in cells after exposure to ionizing radiation. This study will generate quantitative estimates of the efficiency of NB nucleation for different types of radiation, including their kinetics and stability under different conditions. The second Aim is to explore the use of radiation- induced NB to enhance the therapeutic efficacy of RT. Given that exogenously administered NBs are already used to increase the efficacy of high-intensity focused ultrasound (HIFU), intrinsically induced NBs nucleated during exposure to ionizing radiation should have similar enhancing effect for HIFU. Therapeutic efficacy of this combined treatment will be assessed by treating multicellular tumor spheroids sequentially with RT and HIFU, then quantitatively assessing the biological response of the cells. The proposed combination uses treatment modalities approved for use in humans and requires no extrinsic agents to be administered. This combination of radiation-induced NB nucleation and ultrasound-driven NB cavitation is a highly innovative and practical solution to the issue of treatment-resistant tumors.

摘要 该项目研究电离辐射的一个鲜为人知的物理性质，它有可能增加 放射治疗（RT）的有效率。几十年前，人们观察到电离辐射可以 在水和其他液体中成核气体纳米气泡（NB）。精液实验显示NB的存在 在辐照的水中，这表现为实现声学所需的超声功率的降低 气穴现象这些结果提出了一个关键但尚未回答的问题：电离辐射是否使体内的NB成核， 在受辐射的组织中辐射在医学上被广泛使用。NB可能在以下条件下成核的前提是 在诊断扫描或放射治疗期间对患者的影响是重要的，因为NB可能引起生物学效应。 此外，它们在组织中的存在可能会降低声空化的阈值，这表明了一种新的 提高放射治疗效果的机制。该项目的第一个目标是收集严格和 NB在体外辐照细胞中成核的综合证据。灵敏测定，包括暗视野 显微镜和超声成像将用于检测暴露于电离辐射后细胞中的NB。这 这项研究将对不同类型辐射的NB成核效率进行定量估计， 包括它们在不同条件下的动力学和稳定性。第二个目标是探索辐射的使用- 诱导NB以增强RT的治疗功效。鉴于外源性施用的NB已经 用于提高高强度聚焦超声（HIFU）的疗效，固有诱导的NB成核 在暴露于电离辐射期间应具有与HIFU相似的增强效果。本品的治疗效果 联合治疗将通过用RT和HIFU顺序处理多细胞肿瘤球体来评估， 然后定量评估细胞的生物学反应。建议的组合使用治疗 批准用于人类的形式，并且不需要施用外源性试剂。的这种组合 辐射诱导NB成核和超声驱动NB空化是一种高度创新和实用的解决方案 to the issue问题of treatment治疗resistant耐药tumors肿瘤.