临床核医学诊疗中的辐射剂量与防护研究
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摘要
[研究目的]核技术与医学相结合而兴起的核医学已成为现代医学的重要分支学科,为人类的健康诊断与疾病治疗做出了巨大的贡献。但是,临床核医学诊断或治疗对受检者与患者(以下简称“患者”)本身,甚至还可能对相关工作人员以及公众,都潜在一定的辐射危害风险。随着科学技术的不断进步,在临床核医学的快速发展和日益普及应用的当今,很有必要加强对临床核医学的辐射剂量与防护研究工作。本课题在掌握临床核医学的应用及其防护现状基础上,围绕着辐射剂量学这一基础科学问题,针对常用诊疗核素对患者的内照射剂量评估以及患者体外辐射水平等进行了较为深入的研究,旨在为开展临床核医学防护提供科学且实用的理论依据与方法,以更好保护患者、相关工作人员和公众的身体健康。
[研究方法]本课题的主要研究内容包括：1)临床核医学的医疗照射水平分析、2)患者的内照射剂量估算、3)患者的体外辐射水平估算,以及4)相关的辐射防护建议。在医疗照射水平分析研究中,结合上海市临床核医学应用的普查结果和国际放射防护委员会(ICRP)推荐的相关剂量转换系数,开展相关医疗照射所致公众的剂量水平分析。在核医学诊断所致患者的内照射剂量估算研究中,通过建立相关数据库并利用C++程序设计语言,自行编写可同时快速估算患者器官剂量和有效剂量的工具软件；针对最为常见的131I治疗,利用相应的生物代谢模型,通过MATLAB编程计算在甲状腺131I不同吸收分数下,不同性别患者各主要器官/组织的吸收剂量及其变化情况,并首次就膀胱充盈排空行为对相关器官剂量的影响进行理论探讨。在患者的体外辐射水平估算研究中,分别利用点源模型、线源模型和体源模型进行理论计算,再结合临床实际开展验证实验,以获取修正因子的典型值。为提供更加实用的辐射防护建议,针对最常用三种核素(99mTc,18F,131I),利用经修正的线源模型或131I生物代谢模型计算患者体外辐射水平或体内残留活度的变化情况,再结合相关工作人员或公众的受照情形开展剂量评价并提出具体建议。[研究结果]2008年上海市核医学诊断和治疗的应用频率分别为每千人口6.633和0.431人次,远高于“九五”期间的应用频率,肿瘤的PET检查和131I治疗甲状腺癌或甲亢增长速度最快；2008年核医学诊断所致全市居民的人均剂量约为0.032mSv/a。所编写的核医学诊断所致患者内照射剂量估算工具软件可实现患者器官剂量与有效剂量的快速计算,且其计算结果合理。甲状腺癌131I治疗所致患者的膀胱壁、胃壁和小肠的器官剂量可高达1Gy以上且随着甲状腺131I吸收分数的增加而加大,增加排尿频率或合理安排131I药物的服用时间可降低患者主要器官剂量数倍。较之于点源模型,线源模型和体源模型计算得到患者体外辐射水平与实际测量值更为接近；利用线源模型及其相应的修正因子计算得到患者体外1m处的辐射水平与实际测量结果在±30%以内一致。摄入单位活度18F带来患者体外辐射水平高于131I和99mTc分别约为2倍和8倍；相关人员与摄入18F和131I之后的患者近距离接触1h,其所受的辐射剂量均可达0.3mSv。
[结论]临床核医学的应用频率及其所致国民的剂量贡献在不断增加。单次核医学诊断所致患者的全身有效剂量可达几个mSv,甲状腺癌患者接受131I治疗所致膀胱壁、胃壁和小肠的剂量高于1Gy；加快患者体内残留放射性药物的排出,是降低患者辐射危害风险的有效措施。接受18F或131I诊断或治疗的患者体外辐射水平较高,有必要严格控制相关人员与患者的接触时间。
Objective Nuclear medicine has become an important branch of modern medicine, and has made tremendous contributions to the health diagnosis and disease treatment. However, in the practice of clinical nuclear medicine (CNM), the radiation hazards are potential to not only the examinees or patients (hereinafter referred to as "patients"), but also to the related staffs and public. With the continuous progress of science and technology, the development of CNM was very fast and its application frequency has been increasing, therefore, it is necessary to strengthen the researches on radiation protection. Having understood current status on the application of CNM and the facts of radiation protection, and taking the radiation dosimetry as fundamental scientific questions, more in-depth studies on both the internal doses and external doses related with commonly used radionuclides in CNM were conducted in this thesis. The studies were aimed to provide some theoretical basis and measures for practically conducting the radiation protection in CNM, and to further protect patients and the relevant staffs as well as the public from radiation risks.
Methods The main contents of the thesis include:1) analysis of the medical exposure levels,2) theoretical assessments of the internal doses,3) theoretical assessments of the surface radiation levels, and4) recommendations for radiation protection in CNM. The medical exposure levels were studied based on the census data in Shanghai, and the dose conversion factors (DCF) recommended by the International Commission on Radiological Protection (ICRP) were used. For fast estimations of the organ doses and effective doses from diagnostic CNM, a database on the DCF was built, and a calculation tool was developed using C++programming language. For the most commonly used131I in the CNM therapy, based on its biological metabolic model and MATLAB programming, the organ/tissue absorbed doses were calculated for both the male and female in different conditions of thyroid uptake of iodine, and the impacts of bladder filling-emptying process on the organ doses were theoretically discussed. For estimation of the surface radiation levels, theoretical calculations were performed based on the point-source model, the line-source model and the volume-source model, and the correction factors were obtained from the verification experiments. For providing more practical protection measures against the three most commonly used radionuclides (99mTc,18F,131I), theoretical calculations based on the modified line-source model or131I biological metabolic model were used to calculate the surface radiation levels first, and then combined with the exposure situations of relevant staffs or the public, detailed recommendations were made at last.
Results The application frequencies of the diagnostic and therapeutic CNM in Shanghai in2008were6.633and0.431per1,000population, respectively, much higher than those during the "Ninth Five-Year Plan" period. The PET examination for tumors and131I therapy for thyroid cancer or hyperthyroidism increased the fastest. The annual per capita dose for residents in Shanghai was about0.032mSv in2008. The calculation tool developed in this study can simultaneously calculate both the organ doses and effective doses of patients from the diagnostic CNM, and the calculation results are reasonable. The organ doses for bladder, stomach or small intestine are higher than1Gy after the thyroid cancer therapy with131I, and the dose will further increase with the increasing uptake rate of131I in thyroid. An increased urination frequency or a reasonable time arrangement of131I intake will reduce the organ dose for bladder by several times. Compared to using the point-source model, the surface radiation levels could be more accurately estimated by using the line-source model or the volume-source model. The surface radiation levels calculated with the line-source model and its corresponding correction factors are in general agreement with measured values within±30%. For intake of the same activity of radionuclides, the surface radiation level brought by18F is about twice and8times of131I and99mTc in the same point, respectively. The person closely touching with the patient after uptake of18F or131I in an hour will receive about0.2to0.3mSv of additional exposure.
Conclusions The application frequency of CNM and its dose contribution to the public exposure have been increasing. The effective dose to the patient from a single diagnostic CNM procedure is up to several milli-Sievert, and the organ doses for bladder, stomach or small intestine are higher than1Gy in the thyroid cancer therapy with131I. Speeding up the discharge of residual radioactive is an effective way to reduce the by-side radiation risks for the patients. As the surface radiation levels of the patient intake18F or131I in CNM are considerable, it is necessary to strictly control the touching time of relevant personnel with the patient.
[研究方法]本课题的主要研究内容包括：1)临床核医学的医疗照射水平分析、2)患者的内照射剂量估算、3)患者的体外辐射水平估算,以及4)相关的辐射防护建议。在医疗照射水平分析研究中,结合上海市临床核医学应用的普查结果和国际放射防护委员会(ICRP)推荐的相关剂量转换系数,开展相关医疗照射所致公众的剂量水平分析。在核医学诊断所致患者的内照射剂量估算研究中,通过建立相关数据库并利用C++程序设计语言,自行编写可同时快速估算患者器官剂量和有效剂量的工具软件；针对最为常见的131I治疗,利用相应的生物代谢模型,通过MATLAB编程计算在甲状腺131I不同吸收分数下,不同性别患者各主要器官/组织的吸收剂量及其变化情况,并首次就膀胱充盈排空行为对相关器官剂量的影响进行理论探讨。在患者的体外辐射水平估算研究中,分别利用点源模型、线源模型和体源模型进行理论计算,再结合临床实际开展验证实验,以获取修正因子的典型值。为提供更加实用的辐射防护建议,针对最常用三种核素(99mTc,18F,131I),利用经修正的线源模型或131I生物代谢模型计算患者体外辐射水平或体内残留活度的变化情况,再结合相关工作人员或公众的受照情形开展剂量评价并提出具体建议。[研究结果]2008年上海市核医学诊断和治疗的应用频率分别为每千人口6.633和0.431人次,远高于“九五”期间的应用频率,肿瘤的PET检查和131I治疗甲状腺癌或甲亢增长速度最快；2008年核医学诊断所致全市居民的人均剂量约为0.032mSv/a。所编写的核医学诊断所致患者内照射剂量估算工具软件可实现患者器官剂量与有效剂量的快速计算,且其计算结果合理。甲状腺癌131I治疗所致患者的膀胱壁、胃壁和小肠的器官剂量可高达1Gy以上且随着甲状腺131I吸收分数的增加而加大,增加排尿频率或合理安排131I药物的服用时间可降低患者主要器官剂量数倍。较之于点源模型,线源模型和体源模型计算得到患者体外辐射水平与实际测量值更为接近；利用线源模型及其相应的修正因子计算得到患者体外1m处的辐射水平与实际测量结果在±30%以内一致。摄入单位活度18F带来患者体外辐射水平高于131I和99mTc分别约为2倍和8倍；相关人员与摄入18F和131I之后的患者近距离接触1h,其所受的辐射剂量均可达0.3mSv。
[结论]临床核医学的应用频率及其所致国民的剂量贡献在不断增加。单次核医学诊断所致患者的全身有效剂量可达几个mSv,甲状腺癌患者接受131I治疗所致膀胱壁、胃壁和小肠的剂量高于1Gy；加快患者体内残留放射性药物的排出,是降低患者辐射危害风险的有效措施。接受18F或131I诊断或治疗的患者体外辐射水平较高,有必要严格控制相关人员与患者的接触时间。
Objective Nuclear medicine has become an important branch of modern medicine, and has made tremendous contributions to the health diagnosis and disease treatment. However, in the practice of clinical nuclear medicine (CNM), the radiation hazards are potential to not only the examinees or patients (hereinafter referred to as "patients"), but also to the related staffs and public. With the continuous progress of science and technology, the development of CNM was very fast and its application frequency has been increasing, therefore, it is necessary to strengthen the researches on radiation protection. Having understood current status on the application of CNM and the facts of radiation protection, and taking the radiation dosimetry as fundamental scientific questions, more in-depth studies on both the internal doses and external doses related with commonly used radionuclides in CNM were conducted in this thesis. The studies were aimed to provide some theoretical basis and measures for practically conducting the radiation protection in CNM, and to further protect patients and the relevant staffs as well as the public from radiation risks.
Methods The main contents of the thesis include:1) analysis of the medical exposure levels,2) theoretical assessments of the internal doses,3) theoretical assessments of the surface radiation levels, and4) recommendations for radiation protection in CNM. The medical exposure levels were studied based on the census data in Shanghai, and the dose conversion factors (DCF) recommended by the International Commission on Radiological Protection (ICRP) were used. For fast estimations of the organ doses and effective doses from diagnostic CNM, a database on the DCF was built, and a calculation tool was developed using C++programming language. For the most commonly used131I in the CNM therapy, based on its biological metabolic model and MATLAB programming, the organ/tissue absorbed doses were calculated for both the male and female in different conditions of thyroid uptake of iodine, and the impacts of bladder filling-emptying process on the organ doses were theoretically discussed. For estimation of the surface radiation levels, theoretical calculations were performed based on the point-source model, the line-source model and the volume-source model, and the correction factors were obtained from the verification experiments. For providing more practical protection measures against the three most commonly used radionuclides (99mTc,18F,131I), theoretical calculations based on the modified line-source model or131I biological metabolic model were used to calculate the surface radiation levels first, and then combined with the exposure situations of relevant staffs or the public, detailed recommendations were made at last.
Results The application frequencies of the diagnostic and therapeutic CNM in Shanghai in2008were6.633and0.431per1,000population, respectively, much higher than those during the "Ninth Five-Year Plan" period. The PET examination for tumors and131I therapy for thyroid cancer or hyperthyroidism increased the fastest. The annual per capita dose for residents in Shanghai was about0.032mSv in2008. The calculation tool developed in this study can simultaneously calculate both the organ doses and effective doses of patients from the diagnostic CNM, and the calculation results are reasonable. The organ doses for bladder, stomach or small intestine are higher than1Gy after the thyroid cancer therapy with131I, and the dose will further increase with the increasing uptake rate of131I in thyroid. An increased urination frequency or a reasonable time arrangement of131I intake will reduce the organ dose for bladder by several times. Compared to using the point-source model, the surface radiation levels could be more accurately estimated by using the line-source model or the volume-source model. The surface radiation levels calculated with the line-source model and its corresponding correction factors are in general agreement with measured values within±30%. For intake of the same activity of radionuclides, the surface radiation level brought by18F is about twice and8times of131I and99mTc in the same point, respectively. The person closely touching with the patient after uptake of18F or131I in an hour will receive about0.2to0.3mSv of additional exposure.
Conclusions The application frequency of CNM and its dose contribution to the public exposure have been increasing. The effective dose to the patient from a single diagnostic CNM procedure is up to several milli-Sievert, and the organ doses for bladder, stomach or small intestine are higher than1Gy in the thyroid cancer therapy with131I. Speeding up the discharge of residual radioactive is an effective way to reduce the by-side radiation risks for the patients. As the surface radiation levels of the patient intake18F or131I in CNM are considerable, it is necessary to strictly control the touching time of relevant personnel with the patient.
引文
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[9]North DL, Shearer DR, Hennessey JV and Donovan GL. Effective half-life of 131I in thyroid cancer patients [J]. Health Phys.,2001,81(3):325-329.
[10]ICRP. Age-dependent doses to members of the public from intake of radionuclides:part 1 [R]. ICRP Publication 56. Oxford, UK:Pergamon press, 1990.
[11]Lessard ET, Xia YH, et al. Interpretation of bioassay measurements [R]. New York:U.S. Nuclear Regulatory Commission, NUREG/CR-4884,1988.
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[1]Barrington SF, Kettle AG, O'Doherty MJ, Wells CP, Somer EJR, Coakley AJ. Radiation dose rates from patients receiving iodine-131 for carcinoma of the thyroid [J]. Eur. J Nucl. Med.,1996,23:123-130.
[2]卢宁,汪静,乔宏庆,周谊,邓敬兰,李国权.18F-FDG PET显像中受检者周围人员的辐射剂量监测.[J]中华核医学杂志,2004,24(3)：186-188.
[3]石成玉,徐榭,王进亮,白净.新一代虚拟人体解剖模型开发研究及其在放射医学及防护中的应用[J].中华放射医学与防护杂志,2005,25(2)：201-205.
[4]张居营,徐榭,石成玉.四维动态数字人体模型的开发及其在放疗计划中评估器官呼吸运动影响的研究[J].中国医学影像技术,2006,22(9)：1301-1305.
[5]Cristy M, Eckerman K. Specific absorbed f ractions of energy at various ages from internal photons sources [R]. Oak Ridge:Oak Ridge National Laboratory, 1987.
[6]Xu XG, Chao TC, Bozkurt A. VIP-Man:an image-based whole body adult male model constructed from color photographs of the visible human project for multi-particle Monte Carlo calculations [J]. Health Phys,2000,78(5):476-486.
[7]Zhang J, Na Y, Xu X. Development of whole-body phantoms representing an average adult male and female using surface-geometry methods [J]. Med. Phys., 2008,35(6):2875.
[8]Gibbs SJ, Pujol A, Chen TS, et al. Patient risk from interproximal radiography [J]. Oral Surgery, Oral Medicine, Oral Pathology,1984,58(3):347-354.
[9]Williams G, Zankl M, Abmayr W, et al. The calculation of dose from external photon exposures using reference and realistic human phantoms and Monte Carlo methods [J]. Phys. Med. Biol.,1986,31(4):449-452.
[10]Jones DG. A realistic anthropomorphic phantom for calculating organ doses arising from external photon irradiation [J]. Radiat. Prot. Dosim.,1997,72(1): 21-29.
[11]Petoussi-Hen N, Zankl M. Voxel anthropomorphic models as a tool for internal dosimetry [J]. Radiat. Prot. Dosim.,1998,79(1-4):415-418.
[12]Nipper JC, Williams JL, Bolch WE. Creation of two tomographic voxel models of paediatric patients in the first year of life [J]. Phys. Med. Biol.,2002, 47:3143-3164.
[13]ICRP. Adult reference computational phantoms, ICRP Publication 110 [M]. Oxford:Pergamon Press,2009:39-44.
[14]MCNP-a general Monte Carlo N-particle transport code, Version 5 [M]. Los Alamos National Laboratory. Report LA-UR-03-1987 (2003, revised 2004).
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[2]Remy H,Borget I, Leboulleux S, et al.131I effective half-life and dosimetry in thyroid cancer patients [J]. Journal of Nuclear Medicine,2008,49:1445-1450.
[3]AlhajA N, LagardeC S,Lobriguito A M.Patient parameters and other radiation safety issues in 131I therapy for thyroid cancer trement [J]. Health Phys.,2007,93: 656-666.
[4]Willegaignon J, Malvestiti L F, Guimaraes M I C, et al.131I effective half-life (Teff) for patients with thyroid cancer [J]. Health Phys,2006,91:119-122.
[5]NCRP Commentary No.11. Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients [M]. National Council on Radiation Protection and Measurements, February,1995.
[6]潘自强,叶常青,张延生等.GB18871-2002：电离辐射防护与辐射源安全基本标准[B].北京：中国标准出版社,2002.
[7]ICRP. The 2007 Recommendations of the international commission on radiological protection [M]. ICRP Publication 103. Elsevier,2007
[8]EURATOM. Expert group ex/art 31 guidance of radiation protection following Iodine therapy concerning doses due to outpatients or discharged inpatients [R]. Brussels:EURATOM,1997.
[9]ICRP. Release of patients after therapy with unsealed radionuclides. International Commission on Radiological Protection [M]. ICRP Publication 94. Stockholm, Sweden:Elsevier Ltd,2004.