Image-guided Dosimetry for Injectable Brachytherapy based on Elastin-like Polypeptide Nanoparticles

基于类弹性蛋白多肽纳米颗粒的注射近距离放射治疗的图像引导剂量测定

• 批准号: 9530607
• 负责人: Jing Cai
• 金额: $ 16.53万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9530607
• 关键词: Adverse effects; Algorithms; Animals; Behavior; Biopolymers; Brachytherapy; Cancerous; Chemicals; Chronic; Clinical; Computer software; Convolution Kernel; Deposition; Diagnostic Imaging; Diffusion; Dose; Elastin; Environment; Exhibits; Foundations; Genetic Engineering; Goals; Hydrophobicity; Image; Injectable; Injections; Ionizing radiation; Knowledge; Local Therapy; Measurement; Methodology; Methods; Modeling; Modernization; Monte Carlo Method; Nature; Normal tissue morphology; Optics; Outcome; Patients; Performance; Phase Transition; Planning Techniques; Polymers; Positioning Attribute; Procedures; Process; Radiation; Radiation Oncology; Radiation therapy; Radioactive; Radioisotopes; Radiolabeled; Research; Research Infrastructure; Scheme; Science; Science of genetics; Site; Structure; System; Targeted Radiotherapy; Techniques; Temperature; Therapeutic; Tissues; Toxic effect; Yin; analog; aqueous; base; cancer therapy; clinical practice; design; detector; dosimetry; experience; experimental study; image guided; image guided radiation therapy; imaging capabilities; imaging modality; improved; in vivo; nanocrystal; nanoparticle; novel; optical fiber; outcome forecast; polypeptide; pre-clinical; protein aggregation; public health relevance; response; retention rate; treatment planning; tumor

ABSTRACT Elastin-like polypeptides (ELP) present a promising novel mechanism for delivering brachytherapy for cancer treatment. We present a genetically encoded polymer solution, composed of a novel radiolabeled-ELP design that self-assembles upon intratumoral injection. Our preliminary results of small animal studies demonstrate 100% tumor response, effective radionuclide retention rates, strong in vivo depot stability, and no polymer- induced toxicities. While highly promising for improved brachytherapy, the current ELP workflow lacks a dosimetry framework. Without this essential clinical analog, the feasibility of an ELP brachytherapy approach remains indefinitely limited to a pre-clinical environment. The overall objective of this proposal is therefore to provide this critical infrastructure by developing, validating, and evaluating a methodology for determining optimal image-guided dosimetry for ELP-based injectable brachytherapy. This includes implementing modern diagnostic imaging capabilities into the current workflow, developing new dose calculation and optimization schemes that account for the unique nature of ELP dynamics, and designing novel dosimetry verification experiments to validate the process. Aim 1 is to develop a method for image-guided dosimetric planning for injectable ELP brachytherapy. Aim 2 is to evaluate the performance of the developed dosimetric planning methodology. Outcome of the proposed study will provide initial treatment planning, optimization, and verification capabilities for ELP-based procedures. We will fundamentally improve our understanding of ELP dynamics in tissue and its impact on dosimetry. This will transform the way in which ELP procedures are performed in the pre-clinical setting, forming a stronger translational relationship between basic polymer science and clinical radiation oncology. The fully developed methodology will serve as the technical foundation for the biopolymer approach, a necessary component if the technique is to someday be implemented into clinical practice.

抽象的 弹性蛋白样多肽（ELP）提出了一种有希望的新型机制，用于癌症 治疗。我们提出了一种遗传编码的聚合物溶液，该溶液由新型的放射性标记-ELP设计组成 这种自我组装在肿瘤内注射后。我们小动物研究的初步结果表明 100％肿瘤反应，有效放射性核素的保留率，强大的体内仓库稳定性，没有聚合物 - 诱导的毒性。虽然非常有希望改善近距离放射治疗，但目前的ELP工作流缺乏 剂量计框架。没有这种基本的临床类似物，ELP近距离放射治疗方法的可行性 仍然无限期地限于临床前环境。因此，该提议的总体目标是 通过开发，验证和评估确定的方法来提供这种关键的基础架构 最佳图像引导的剂量测定法，用于基于ELP的可注射近距离放射治疗。这包括实施现代 诊断成像功能到当前工作流程，开发新的剂量计算和优化 说明ELP动态的独特性质并设计新颖的剂量验证的方案 实验以验证该过程。目标1是开发一种图像引导的剂量计计划的方法 可注射的ELP近距离放射治疗。 AIM 2是评估发达的剂量计划的性能 方法论。拟议研究的结果将提供初始的治疗计划，优化和 基于ELP的程序的验证功能。我们将从根本上提高我们对ELP的理解 组织中的动力学及其对剂量法的影响。这将改变ELP程序的方式 在临床前的环境中进行，形成基本聚合物之间的更强的翻译关系 科学和临床辐射肿瘤学。完全开发的方法将作为技术基础 对于生物聚合物方法，如果有一天将其实施到该技术中，则是必要的组成部分 临床实践。