原位高灵敏水凝胶放疗剂量计的构建

In-situ measurement of the energy of ionizing radiation (or doses) at the tumors and surrounding healthy tissues is a straightforward approach to estimate and optimize treatment planning system, and thus facilitate the radiotherapy process. Currently, the in-situ dosimeters in radiotherapy feature undesirable sensitivity to doses, lack of tissue equivalent and are not easy to construct and manipulate. In this proposal, therefore, we plan to construct hydrogel-based dosimeters for the in-situ measurement of doses during radiotherapy process. The main characteristic of this project is to make the dosimeters sensing the environmental change (the generation of hydroxyl radicals) caused by the ionizing radiation. We will introduce sensitive fluorescence probes of hydroxyl radicals into the hydrogel matrix, which is strongly required to feature desirable mechanical strength and adhesion characteristics for the utilization in clinics. We will further move to improve the accuracy and sensitivity of the dosimeters by the introduction of a second reference fluorescent monomer as a ratiometric probe, and by the elaboration of physicochemical properties of the dosimeters. The latter will be realized via the incorporation of fluorescence resonance energy transfer effect and the matrix of photonic crystals. Ultimately, our device will aim to in-situ measure dose of radiotherapy with high accuracy and sensitivity, by bonding to the patients' skin or in vivo implanting towards the expected position. By combining Monte Carlo simulation, image analysis and the measurment of absolute doses, the accuracy of our dosimeters will be verified. This project will provide a novel and effective clue for the study of hydrogel-based dosimeters in radiotherapy.

原位测量肿瘤及其附近健康组织吸收的电离辐射能量（即剂量，J/Kg），是验证和优化放疗治疗计划最直接的方法，是把控整个放疗过程的关键。针对目前原位放疗剂量计灵敏度不高、组织等效差、制备和使用困难等缺点，本项目拟利用放疗过程中电离辐射致水局部产生自由基这一微环境变化为特点，以具有合适的力学强度和组织黏附性能的非共价键交联水凝胶为基质材料，在其骨架中引入检测羟基自由基单体作为探针，构筑对放疗剂量具有高灵敏度检测的水凝胶剂量计材料。辅以第二荧光单元作为“内嵌式”比色矫正因子，以及化学和/或结构信号增强材料设计，最终通过粘附在患者体表或后装等导管方式放置在体内的特定位置，实现原位剂量测量的、具有高灵敏度和准确性的水凝胶放疗剂量计。通过模拟计算、图像分析和绝对剂量测量，验证材料测量准确性。本项目将为放疗剂量计材料的研究开辟一条全新而高效的途径。

原位测量肿瘤及其附近健康组织吸收的电离辐射能量（即剂量，J/Kg），是验证和优化治疗计划最直接的方法，就能把控整个放疗过程。针对目前原位放疗剂量计制备和使用困难、组织等效差、灵敏度不高等缺点，本项目针对放疗过程中电离辐射致水局部产生自由基这一微环境变化为特点，以具有合适的力学强度和组织黏附性能的非共价键交联水凝胶和微凝胶、纳米凝胶为基质材料，在其骨架中引入检测羟基自由基单体（包括：香豆素-3-羧酸、氨基苯基荧光素和羟基苯基荧光素）作为探针，构筑对放疗剂量具有高灵敏度检测的水凝胶剂量计。辅以第二荧光单元作为“内嵌式”比色矫正因子，最终通过在体模表面或后装等导管方式放置在体内的特定位置，实现1D/2D原位剂量测量的、剂量测量范围0-20Gy,最低检测下限0.5Gy。能够满足临床不同射线（X射线、电子束和γ射线）下剂量响应要求。，剂量计在25-65 oC温度内具有较好的稳定性，温度的不确定度为0.1%。同时，还具有较好的时间稳定性，剂量测量信息可以保存5周，时间的不确定度为1.9%。通过与模拟计算、图像分析、绝对剂量和临床治疗计划系统等数据相比较，我们的剂量计具有验证剂量计测量准确性。本项目将为原位放疗剂量计的研究开辟一条全新而高效的途径。