核医学诊断操作中的亚细胞水平吸收剂量及其生物效应

许多诊断用的放射性核素,在诊断过程中同时伴有俄歇电子发生,这些单能电子引起了亚细胞水平的剂量分布不均,并且当这些俄歇电子参入DNA时引起严重放射生物学毒性,其相对生物效应大于1。为此,根据放射性药物在亚细胞分布提出了恰当的剂量计算模型（细胞型或传统型MIRD）,讨论了设计新的放射性诊断药物的核素的选择及其原则。     

核医学诊断操作中的亚细胞水平吸收剂量及其生物效应

许多诊断用的放射性核素,在诊断过程中同时伴有俄歇电子发出,这些单能电子引起了亚细胞水平的剂量分布不均,并且当这些俄歇电子参入DNA时引起严重放射生物学毒性,其相对生物效应大于1.为此,根据放射性药物在亚细胞分布提出了恰当的剂量计算模型(细胞型或传统型MIRD),讨论了设计新的放射性诊断药物时核素的选择及其原则。     

α核素非均匀微观分布对细胞微剂量的影响

目的探讨放射免疫治疗中α核素在细胞水平上非均匀微观分布对细胞S因子的影响。方法利用蒙特卡罗方法随机模拟α粒子的发射;基于连续慢化近似模型,根据α粒子剩余射程-能量的关系,采用插值法计算α粒子入射动能和出射动能,得到其在靶区内的能量沉积。以213Po为例,计算了不同细胞大小及核素不同微观分布（均匀分布、中心分布、随核素距细胞中心的距离线性递增、线性递减、指数递增、指数递减）下细胞对细胞的S因子。结果213Po均匀分布下的S（C←C）与Hamacher给出的结果符合得很好;不同微分布下的S（C←C）有显著差别。分析表明,核素不同微观分布所造成的α粒子在靶区内运动的平均弦长的显著变化,以及由此产生的α粒子平均碰撞阻止本领的变化,是造成细胞S因子有显著差别的主要原因。结论放射性核素非均匀微分布类型显著影响细胞S因子的大小,在估算细胞吸收剂量时应予以重视。     

氚β粒子所致的细胞核剂量

本文给出了氚目粒子所致的细胞核平均吸收剂量的计算方法和细胞核剂量的微观统计分布,讨论了器官平均剂量与细胞核平均剂量的关系。这些资料对低剂量水平的氚效应的研究有一定的参考价值。     

用能量沉积核函数方法计算~(60)Co照射野的吸收剂量

目的　介绍了用能量沉积核函数方法计算60 Co照射野吸收剂量的方法。方法　能量沉积核函数方法将吸收剂量的贡献分为 3部分 :原射线、单次散射和多次散射。它使用基本的剂量学数据 ,如射野中心轴百分深度剂量、离轴比和准直系统散射输出因子等 ,这些数据在Fyc 5 0H治疗机上用方形照射野测量得到。再用能量沉积核函数计算吸收剂量。并讨论了散射线对吸收剂量的影响。结果　从测量数据得到了原射线和散射线的能量沉积核函数 ,并利用能量沉积核函数计算60 Co照射野的主要剂量学参数 ,计算值和测量值是一致的 ;不规则照射野的吸收剂量及其分布的计算结果也和测量结果符合得很好。结论　能量沉积核函数方法适用于较精确地计算60 Co不规则照射野的吸收剂量。     

用能量沉积核函数方法计算60Co照射野的吸收剂量

目的 介绍了用能量沉积核函数方法计算＾６０Ｃｏ照射野吸收剂理的方法。方法 能量沉积核函数方法将吸收剂量的贡献分为３部分：原射线、单次散射和多次散射。它使用基本的剂量学数据,如射野中心轴百分深度剂量、离轴比和淮直系统散射输出因子等,这些数据在Ｆｙｃ５０Ｈ治疗机上用方形照射野测量得到,再用能量沉积核函数计算吸收剂量,并讨论了散射线对吸收剂量的影响。结果 从测量数据得到了原射线和散射线的能量沉积核函数,并利用能量沉积核函数计算＾６０Ｃｏ照射野的主要剂量学参数。计算值和测量值是一致的;不规则照射野的吸收剂量及其分布的计算结果也和测量结果符合得很好。结论 能量沉积核函数方法适用于较精确地计算＾６０Ｃｏ不规则照射野的吸收剂量。     

99mTc-DTPA细胞水平分布的实验研究

目的核医学中传统的MIRD剂量估算方法是假设放射性药物在器官内均匀分布,用器官的平均剂量描述每个细胞及细胞核的剂量.基于核素的微观分布数据,建立微剂量的剂量估算模式,从而为核医学中诊疗计划的制定、放射药物效果和危害的预测及评价、分子核医学研究提供基础的微剂量估算及其分布研究的方法和基础数据.方法采用了放射自显影术和冰冻切片技术,建立自显影银颗粒密度与放射性药物强度的刻度曲线,确定放射性药物99mTc-DTPA的微观分布.结果银颗粒密度与施入比活度的相关系数为0.9915,刻度系数为6.48×10-5Bq.细胞浆与细胞核的分布比为1.78.结论放射性药物在细胞水平的分布是不均匀的,因此在计算细胞水平的剂量时应考虑到其分布的不均匀性.     

α粒子内照射致细胞失活的模型

通过理论模型研究了均匀和非均匀分布在细胞周围发射α粒子的放射性免疫结合物的能量沉积分布,计算了细胞核的能量沉积谱,并将其用于估算简单的生物学模型细胞活存份额。实验运用Monte-Carlo模拟技术,假设放射源按三种几何形式分布,井用其相对比例表征:①在介质中均匀地分布;②在细胞表面结合分布;③在细胞浆中均匀地分布。考虑到能量沉积的涨落,利用Roesch提出的内照射微剂量学理论,模拟计算细胞核的比能谱f(z)。用下述生物学模型依据每个细胞归一的比能分布估算细胞活存份额。通常,细胞群体     

组织等效介质中正离子径迹周围剂量分布特性研究

目的探讨正离子在人体组织（或组织等效介质）中能量沉积的微观特性。方法在对人体组织材料进行分析的基础上,确定了密度为1g/cm^3水蒸汽作为组织等效材料的合理性,利用MC粒子输运技术模拟了质子在介质中的微观行为。通过对计算所得数据进行系统分析,得出正离子在组织等效材料中能量沉积微观特性的一些规律与特点。结果在介质中正离子除使原子激发损失能量之外,还会通过电离的方式,把其能量交给次级电子,最后由电子完成其能量沉积过程。所以,正离子在介质中发生能量沉积时,大部分能量沉积在径迹芯上,次级电子主要在径迹芯以外发生能量沉积,从而在介质中形成特定的剂量分布形式。结论正离子在介质中产生的剂量分布研究对于探讨辐射生物效应具有重大意义。     

~(67)Ga和其他俄歇发射放射性核素在人和动物组织的亚细胞分布

目的 :为评价俄歇发射放射性核素的生物效应 ,需要发展适用的俄歇电子剂量学 ,为此需要清楚了解核素在亚细胞水平的生物学分布和动态变化 ,从而开展了在人和动物静脉注入肿瘤定位药物 6 7Ga-柠檬酸盐后在肿瘤和正常组织亚细胞分布的研究。方法 :临床研究是在静脉注射放射性核素后不同时间取少量肿瘤或正常组织活检标本 ,立即放入冰盒内送往实验室 ;动物实验按研究计划在注入药物后不同时间杀死动物 ,取出需要的组织样品。样品组织均浆后分离亚细胞成分 ,分离的每一成分用γ谱仪进行测量 ,并测定蛋白含量、溶酶体标志酶芳基硫酸酯酶、线粒体…     

贴壁细胞β射线内照射吸收剂量的计算

目的：寻求贴壁细胞β射线内照射吸收剂量的计算公式。方法：根据辐射吸收剂量定义和MIRD方案进行推导。从悬浮细胞培养模式入手,考虑到贴壁细胞培养的特殊性,以及其受照射的方向,依据累积放射性活度、β射线能量、培养液质量计算辐吸收剂量。结果：得到悬浮细胞、贴壁细胞β射线内照射吸收剂量的计算公式。并进行计算验证。结论：该公式使用简便,可靠性强,准确性好,便于实际应用。     

Radiotoxicity of 125I-iododeoxyuridine in pre-implantation mouse embryos.

The radiotoxicity of DNA incorporated 125I in cultured pre-implantation two-cell mouse embryos was investigated and compared with external gamma-irradiation. The uptake of 125IdU in the two-cell stage embryos was determined as a function of incubation time and concentration of radioactivity (MBq/ml) in the medium. The absorbed dose to the embryos was calculated using conventional procedures. The embryo survival curves show that the dose at 37% survival is only about 15 cGy for 125IdU, whereas for 137Cs-photons it is 175 cGy. The extreme toxicity observed is thought to be due to the localized energy deposition of the numerous low energy Auger electrons emitted in the decay of 125I. These results are consistent with earlier observations in mouse testis and cultured cells and point to the need for assessing the radiation risk from incorporated Auger electron emitting radionuclides based on their subcellular distribution.     

Radiotoxicity of 125I-Iododeoxyuridine in Pre-implantation Mouse Embryos

Summary

The radiotoxicity of DNA incorporated ¹²⁵I in cultured pre-implantation two-cell mouse embryos was investigated and compared with external γ-irradiation. The uptake of ¹²⁵IdU in the two-cell stage embryos was determined as a function of incubation time and concentration of radioactivity (MBq/ml) in the medium. The absorbed dose to the embryos was calculated using conventional procedures. The embryo survival curves show that the dose at 37% survival is only about 15 cGy for ¹²⁵IdU, whereas for ¹³⁷Cs-photons it is 175 cGy. The extreme toxicity observed is thought to be due to the localized energy deposition of the numerous low energy Auger electrons emitted in the decay of ¹²⁵I. These results are consistent with earlier observations in mouse testis and cultured cells and point to the need for assessing the radiation risk from incorporated Auger electron emitting radionuclides based on their subcellular distribution.     

Dosimetry at the cellular level of Kupffer cells after technetium-99m-sulphur colloid injection.

The radiation dose to Kupffer cells was estimated at the cellular level after intravenous injection of 99mTc labeled sulphur colloids in rats. The results were then compared with those obtained using macroscopic dosimetry. From the microscopy appearance observed using a "track" microautoradiographic method (MAR), it was shown that only 0.2% of the Kupffer cells were actually involved in the pinocytosis of radioactive colloids. For each electronic emission from 99mTc (Auger and internal conversion), the fraction of the emitted energy actually absorbed within the Kupffer cell was calculated using the values provided by Berger. About 15% of the total energy emitted by electrons was absorbed in 0.2% of the Kupffer cells. If these results are extrapolated to humans, the dose absorbed by the labeled cells can be estimated to be between 0.5 and 0.9 Gy/MBq. This represents about 15,000 times the average electron dose to the liver as estimated from macrodosimetric methods. In cases such as this one where an important distribution heterogeneity is expected, dosimetric estimations at a cellular level may be particularly useful.     

In vivo effects of iron-55 and iron-59 on mouse testes: biophysical dosimetry of Auger electrons

When the Auger-electron emitter, 55Fe, and the beta-emitter, 59Fe, are similarly distributed in the testes of mice, the conventionally calculated average radiation dose to the organ from 55Fe is about 2.6 times more effective in reducing the sperm-head count than the dose from 59Fe. This finding emphasizes the ability of low-energy Auger electrons to damage radiosensitive targets of cells through localized irradiation. The observed efficacy is understandable in terms of dosimetric models based on intracellular distribution studies of the radionuclides.     

Cell Irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings.Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.     

Some microdosmetric data on Astatine-211.

Radionuclides which emit short range, high LET radiations such as alpha and Auger electrons have very promising applications in cancer therapy. Such radionuclides should eventually be incorporated into cell nuclei to achieve high radiotoxic effectiveness. This means that the dose distribution within the cell nucleus at microscopic levels is very important for comparison of the real differences between the radiotoxic effectiveness of different radionuclides. An experimental setup to determine real dose absorption on the microscopic scale is extremely difficult to design. For this reason, calculation procedures for microscopic dose absorption are of special interest for the diagnostic and therapeutic applications of radionuclides which emit short-range and high LET radiations. A specific calculation method for microscopic energy absorptions within the cell nucleus from Auger electrons of 125I was described earlier. In this study, the radiotoxic effectiveness of 211At and 125I has been compared using the data obtained by this calculation method. The data obtained show clearly that the radiotoxicity of the alpha and Auger emitter radionuclide 211At is comparable to that of 125I.     

Cell irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings. Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.     

Absorbed dose estimates at the cellular level for I

Microdosimetric calculations of ¹³¹I have been evaluated for a single cell and for cell clusters. A VsBasic program has been used to calculate stopping power, linear energy transfer, range values and deposited energies per decay for beta particles, Auger and conversion electrons of ¹³¹I. The chemical composition of the cell has been taken into account in this model; results were compared with water medium. Besides, total absorbed doses have been calculated for the radionuclides distributed randomly within the cell and clusters. Cross-fire irradiation has been considered for clusters of cells. In this case, absorbed doses per cell within a cluster were found to be significantly higher than absorbed doses per single cell, depending on the cluster size. Results showed that ¹³¹I is a promising radionuclide for therapy of tumors from millimeter to centimeter dimensions.     

Small-scale dosimetry: challenges and future directions

The increased specificity of targeting agents has resulted in an interest in the use of radionuclides that emit particulate radiation: alpha particles, beta particles and Auger electrons. The potential advantage of these radionuclides is the ability to deliver therapeutic doses to individual tumor cells while minimizing the dose to the surrounding normal tissues. However, the dosimetry of these radionuclides is challenging because the dose must be characterized on a scale that is comparable to the range of these emissions, ie, millimeters for beta particles, micrometers for alpha particles, and nanometers for Auger electrons to. In this review, each class of particulate emitter is discussed along with the associated dosimetric techniques unique to calculating dose on these scales. The limitations of these approaches and the factors that hinder the clinical use of small-scale dosimetry are also discussed.