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

摘要 弹性蛋白样多肽（ELP）为肿瘤近距离放射治疗提供了一种有前途的新机制 治疗我们提出了一种基因编码的聚合物溶液，由一种新的放射性标记的ELP设计组成 在瘤内注射后自我组装。我们对小动物的初步研究结果表明， 100%的肿瘤缓解率，有效的放射性核素保留率，强的体内储库稳定性，并且没有聚合物- 诱发毒性。虽然对于改进的近距离放射治疗非常有希望，但当前的ELP工作流程缺乏 剂量学框架如果没有这种基本的临床模拟，ELP近距离放射治疗方法的可行性 仍然无限期地局限于临床前环境。因此，本建议的总体目标是 通过开发、验证和评估用于确定 基于ELP的可注射近距离放射治疗的最佳图像引导剂量测定。其中包括实施现代 诊断成像功能纳入当前工作流程，开发新的剂量计算和优化 计划，占ELP动力学的独特性质，并设计新的剂量学验证 实验来验证这个过程。目的1是开发一种图像引导的剂量计划方法， 可注射ELP近距离放射治疗。目的2是评价所开发的剂量学计划的性能 方法论拟议研究的结果将提供初始治疗计划、优化和 基于ELP的程序的验证能力。我们将从根本上提高我们对ELP的认识 组织动力学及其对剂量测定的影响。这将改变ELP程序的方式， 在临床前环境中进行，在基本聚合物之间形成更强的翻译关系， 科学和临床放射肿瘤学充分开发的方法将作为技术基础 对于生物聚合物方法，如果该技术有一天被实施到 临床实践

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.