基于磁珠时间分辨荧光免疫分析技术的精准给药监测平台的研究及临床初步应用

Precision medicine has been the development trend. However, drug monitoring as an effective tool to promote precision medicine hasn’t been used universally in clinical. The main restrictions are the lack of comprehensive individualized medicine research and appropriate detection technology. Therefore, it is of great significance for us to further study the more precision time-resolved fluorescence immunoassay (TRFIA) and to apply it to the field of drug monitoring to promote the practice and realization of precision medicine. Now, with the aging of the population and the increase of cancer susceptible population, the future demand for chemo drugs will continue to rise. Based on the characteristics of chemo drugs, it is urgently needed to achieve precision medication by the application of drug monitoring. The aim of this study is to apply magnetic bead TRFIA to drug monitoring of chemo drugs, and to analyze the individualized dosing regimen based on the development of analysis technology for drugs, drugs with drug metabolizing enzymes and the combined detection of tumor markers. This work will auxiliary establish the appropriate optimal dosing regimen and therapeutic index reference guide for different population traits by those clinical data of individual area under the concentration time curve and steady-state plasma concentration, and provide technical basis for the establishment of a monitoring platform for precision medication with independent property rights.

精准医疗已是当今医疗发展趋势，而药物监测作为推动精准医疗的有效手段却迟迟未能在临床得以普及，其主要原因是缺乏全面的个体化给药研究数据及适宜的检测分析技术。因此深入研究具备较高精准性能的时间分辨荧光免疫分析技术并将其创新应用于药物监测领域对于推动精准医疗的实践与实现有着实质性的意义。而如今随着人口的老龄化以及癌症易感人群的增加，未来对于化疗药物的需求将不断上升。基于化疗药物的特性采用药物监测来实现精准给药迫在眉急。项目拟通过技术创新，将磁珠时间分辨应用于化疗药物的药物监测，通过研发药物，药物与药物代谢相关蛋白酶类联合以及肿瘤相关抗原联合的检测分析技术来分析个体化给药方案，进一步丰富个体药时曲线下面积及稳态血药浓度等数据辅助确立适宜不同特质人群的最佳给药方案以及治疗指数参考指南，并为建立具备自主产权的临床精准给药监测平台提供技术基础。

精准医疗是当今医疗发展趋势，药物监测作为推动精准医疗的有效手段却迟迟未能在临床得以普及，主要原因是缺乏全面的个体化给药研究及适宜的检测分析技术。因此深入研究具备较高精准性能的时间分辨荧光免疫分析技术并将其创新应用于药物监测领域对于推动精准医疗的实践与实现有着实质性的意义。而如今随着人口的老龄化以及癌症易感人群的增加，未来对于化疗药物的需求将不断上升。基于化疗药物的特性采用药物监测来实现精准给药迫在眉急。项目通过摸索优化小分子药物偶联方案制备有效免疫抗原，采用经典方案免疫小鼠制备筛选阿霉素，紫杉醇及5-氟尿嘧啶单克隆抗体，同时采用磁珠偶联抗体制固定相提高试剂分析性能，建立阿霉素单标记，紫杉醇与5-氟尿嘧啶双标记及5-氟尿嘧啶与和二氢嘧啶脱氢酶双标记磁珠时间分辨免疫分析技术，将时间分辨荧光免疫分析技术应用于化疗药物的药物浓度监测，获取个体药时曲线下面积及稳态血药浓度等数据辅助确立适宜不同特质人群的最佳给药方案以及治疗指数参考指南，并为建立具备自主产权的临床精准给药监测平台提供技术基础。