一种放射性显影剂的血管刺激性评价及人员辐射防护实践
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摘要
目的评价一种锝(99m Tc)标记的放射性显影剂的血管性刺激性,并对放射性药物临床前毒理研究中人员辐射防护提出建议。方法对6只新西兰兔静脉注射锝(99mTc)喷替酸盐注射液,评价其血管刺激性,分析实验前后受试物的比活度和放射化学纯度,实验中对主要操作人员进行剂量监测及表面污染监测。结果实验以临床静脉注射最大浓度555 MBq·m L-1,剂量194 MBq·kg~(-1)(临床最大剂量的21倍)静脉给予兔耳缘静脉后未出现药物相关性血管刺激,给药前后受试物的比活度及放射化学纯度均符合要求,所有操作人员个人单次实验有效剂量最大值0.01 m Sv,预估个人年总有效剂量不超过1 m Sv,小于职业照射人员年有效剂量限值20 m Sv。实验后,人员体表及设备表面均未检测到放射性污染。结论放射性药物非临床毒理研究应根据核素性质及标记底物进行合理的剂量设计和防护措施规划,保证实验结果有效性和安全性的同时,严格执行个人剂量监测和污染监测,保障人员辐射安全。
Objective To evaluate the vascular irritation of a 99 m Tc labeled radiocontrast medium, so as to make suggestions on radioprotection for personnel in the preclinical toxicological study of radiopharmaceuticals. Methods Six New Zealand rabbits were injected with technetium pentetate injection. The specific activity and radiochemical purity of the samples at the start and end of the test were analyzed, and the vascular irritation to the vein was evaluated. Dose monitoring and surface contamination monitoring were carried out during the main processes of the test. Results The maximum concentration of 555 MBq·m L-1 and the dose of 194 MBq·kg~(-1)(21 times of the maximum clinical dose)were intravenously administered through the ear-vein of rabbits. There wasn't drug-related vascular stimulation reactions observed in the test. The detection results of samples' specific activity and radiochemical purity both met the test requirements. The individual highest radiation effective dose of single test of all operators was 0.01 m Sv.The estimated annual total radiation effective dose is not more than 1 m Sv, which is less than the limit of occupational personnel radiation effective dose(20 m Sv). What's more, there was no radioactive contamination detected on surface of operators and equipments. Conclusion During the non-clinical toxicological study of radiopharmaceuticals, rational dose design and protective measures should be carried out according to the nature of nuclides and labelled substrates.It could ensure the safety and efficiency of the experimental results. And at the same time, individual dose monitoring and pollution monitoring should be strictly carried out to ensure the radiation safety of operators.
Objective To evaluate the vascular irritation of a 99 m Tc labeled radiocontrast medium, so as to make suggestions on radioprotection for personnel in the preclinical toxicological study of radiopharmaceuticals. Methods Six New Zealand rabbits were injected with technetium pentetate injection. The specific activity and radiochemical purity of the samples at the start and end of the test were analyzed, and the vascular irritation to the vein was evaluated. Dose monitoring and surface contamination monitoring were carried out during the main processes of the test. Results The maximum concentration of 555 MBq·m L-1 and the dose of 194 MBq·kg~(-1)(21 times of the maximum clinical dose)were intravenously administered through the ear-vein of rabbits. There wasn't drug-related vascular stimulation reactions observed in the test. The detection results of samples' specific activity and radiochemical purity both met the test requirements. The individual highest radiation effective dose of single test of all operators was 0.01 m Sv.The estimated annual total radiation effective dose is not more than 1 m Sv, which is less than the limit of occupational personnel radiation effective dose(20 m Sv). What's more, there was no radioactive contamination detected on surface of operators and equipments. Conclusion During the non-clinical toxicological study of radiopharmaceuticals, rational dose design and protective measures should be carried out according to the nature of nuclides and labelled substrates.It could ensure the safety and efficiency of the experimental results. And at the same time, individual dose monitoring and pollution monitoring should be strictly carried out to ensure the radiation safety of operators.
引文
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[2]国家药典委员会.中华人民共和国药典(四部)[M].北京:中国医药科技出版社, 2015:410-411.
[3] CFDA.药品注册管理办法(局令第28号)化学药品注册分类及申报[EB/OL].(2007-06-18)[2018-12-21]. http://samr.cfda.gov.cn/WS01/CL1031/24529.html.
[4] CFDA.药物刺激性、过敏性和溶血性研究技术指导原则[EB/OL].(2014-05-13)[2018-12-21]..http://www.cde.org.cn/zdyz.do?method=large Page&id=188.
[5]原子高科股份有有限公司.高锝[99mTc]酸钠注射液说明书[Z].2015版.
[6]国家卫生部.电离辐射防护与辐射源安全基本标准[S/OL].(2002-10-08)[2018-12-21]. http://www.moh.gov.cn/zhuz/pcrb/201410/5fffe01da4634747918d15662d3d22ae.shtml.
[7]国家卫生和计划生育委员会.职业性外照射个人监测规范[S/OL].(2016-07-14)[2018-12-21].http://www.moh.gov.cn/zwgkzt/pcrb/201607/e7a42b3ba5a84797826d9c4174a89343.shtml.
[8]光红梅,王庆利. EMA对放射性诊断药品的非临床评价要求介绍[J].中国新药杂志,2018,27(18):2111-2115.
[9]国家药典委员会.中华人民共和国药典(二部)[M].北京:中国医药科技出版社,2015.
[10] EMA. Concept paper on the development of guidance on the nonclinical evaluation of radiopharmaceuticals[S/OL].(2017-09-11)[2018-12-21]. https://www.gmp-compliance.org/gmpnew/.
[11]高婧,杨悦.美国提高新药审评效率的审评模式改进与思考[J].中国药物警戒,2015, 12(8):471-475.
[12]高婧,刘思齐,杨悦.美国药品标准管理模式研究[J].中国药物警戒, 2014, 11(10):606-610.
[13]赖亚辉,王明华.放射防护学[M].北京:中国医药科技出版社,2007:203-205.
[14]郑钧正.电离辐射医学应用的防护与安全[M].北京:原子能出版社,2009:72-273.
[15]安全,张伟,秦秀军,等.放射性药物安全评价实验室的防护与管理[J].癌变·畸变·突变,2014,26(2):154-156.