Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [^99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [^99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [^99mTc]Tc-ZHER2:V2 and [^99mTc]Tc-ZHER2:2395. [^99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [^99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with ^99mTc using a GGGC chelator. The new probe, [^99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [^99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.     

纳米零价铁材料对放射性核素的 去除及机理研究进展

随着人类社会的发展，放射性铀矿的开采和使用越来越多，环境面临着越来越严重的放射性污染问题。从生物和环境的角度来看，有效地清除环境中的放射性核素是核能利用过程中最重要的问题之一。纳米零价铁（nanoscale zero valent iron, nZVI）具有较大的比表面积和较高的活性位点，能显著提高放射性污染物的修复效率。本综述的目的是展示nZVI基材料对放射性核素的高效去除能力和环境修复作用。简介了常用的nZVI基材料（表面改性或多孔材料支撑的nZVI材料）及其对放射性核素的去除效果和相互作用机制（如吸附和氧化还原）。最后，对nZVI材料的应用和挑战给出个人见解。本综述有助于为高效去除放射性核素的nZVI材料的设计指明方向，为放射性核素的高效处理处置提供新材料。     

放射性核素在矿物表面的吸附微观结构分析进展

放射性核素在矿物表面的吸附行为是影响其在环境中的浓度、迁移、转化及毒性的重要过程。本文简要介绍了放射性核素在吸附剂表面的吸附、沉淀、氧化还原反应的作用机理，针对放射性核素在矿物表面的微观吸附形态的研究中所使用的一些先进的实验分析方法，重点介绍了同步辐射X射线吸收精细结构（XAFS）技术、荧光分析以及理论计算等技术，并展望了放射性核素在矿物表面微观反应机制的研究趋势。     

A priori risk-informed approach to ensure the compliance with discharge limits for liquid radioactive effluent to be discharged from APR 1400

ABSTRACT

In order to develop a methodology to guarantee the conformance to operational discharge limits for liquid effluent from a NPP at an early stage of design, a risk-informed approach was proposed and its applicability was verified for APR 1400. Existing methodology to calculate risk-based detection limit for a single radionuclide was improved by incorporating a new model to derive more realistic pathway dose factors. A new simple expression was also proposed to adjust risk-based detection limits for multiple radionuclides mixture if necessary. In addition, a new procedure to warrant the compliance with discharge limits by controlling detection limits of only a few principal radionuclides was established in accordance with risk-informed concept. Through case studies for APR 1400 to be commissioned at a hypothetical site, it was shown that calculated pathway dose factors are more realistic for majority of radionuclides. It also turns out that neither present detection limits nor unadjusted risk-based detection limits can be justified when the radionuclide composition is unknown, however further adjustment of detection limits or increasing additional dilution factor resolves the problem. Finally, ten principal radionuclides were identified and shown to be enough for liquid effluent control at APR 1400 from a risk-informed point of view.     

靶向CD93分子探针制备及其生物学实验研究

CD93分子作为一种新型新生血管生成激活剂,有可能成为肿瘤监测的重要分子靶点,因此制备125I标记抗CD93单抗(125I-anti-CD93 mAb),研究其在荷瘤鼠体内生物学分布及磷屏显像特点,探讨其对A549肺癌靶向性及CD93阳性肿瘤监测的可行性。本文制备125I-anti-CD93 mAb及125I-IgG并进行鉴定;建立A549肺癌荷瘤小鼠模型,经尾静脉注射125I标记抗CD93单抗,并设125I-IgG为对照组,注药后不同时间进行生物学分布及磷屏放射自显影;肿瘤组织行HE染色及CD93免疫组织化学染色;采用统计软件对定量数据(x+s)进行统计学处理,组间数据用t检验,P<0.05为差异有统计学意义。结果表明,125I-anti-CD93 mAb及125I-IgG标记率、放射性比活度、放化纯度分别为91.37%和90.24%,1096.44 MBq/mg和1082.88 MBq/mg,96.49%和94.82%,放置72 h后两标记物的稳定性仍>90%,两者间无统计学差异(生理盐水组P=0.93,t=0.09,血清组P=0.13,t=1.90)。荷瘤鼠生物学分布结果显示125I-anti-CD93 mAb主要经肝肾代谢,注射后48 h时肿瘤组织放射性摄取率为(6.42±0.71)%ID/g,T/NT(瘤/对侧肌肉)摄取比值为4.45±0.86,显著高于对照组125I-IgG组(2.45±0.33/1.71±0.24),P<0.05,t=3.07和P<0.01,t=5.10。动态全身磷屏自显影结果可见,24 h两组小鼠轮廓清楚,48 h时实验组肿瘤显像最清晰,肿瘤放射性摄取比(肿瘤/对侧肌肉)为3.34±0.18,明显高于对照组(1.62±0.19),P<0.01,t=6.52。免疫组化染色结果证实肿瘤高表达CD93。125I-anti-CD93 mAb制备简便,对A549肺癌组织靶向性好,有望成为CD93阳性肿瘤监测的新型分子探针。     

Uptake of Radionuclides onto Suspended Particulate Matter in Coastal Water

Distribution coefficients K _ds of several radionuclides on suspended particulate matter (SPM) have been determined with laboratory batch experiments using samples collected in the Kinki district, Japan. Most SPM in coastal water was retained on the initial filter of four sequential filtering stages (20, 5, 1 and 0.45 μm pore size), maximum K _d also being found for the SPM retained in this first stage. When the filtrations were not performed in series, however, but were conducted from the same tracer solution in parallel, the K _d values were identical for the smaller filter sizes (5, 1 and 0.45 μm) and were greater, by ca. 150% than those derived from the 20 μm filter. The degree of association of the radionuclides with SPM was ⁸⁵Sr<¹³⁷Cs<⁶⁵Zn<⁵⁴Mn<⁶⁰Co. The particulate radioactivity fraction of the SPM in coastal water was estimated at most 0.1 for radionuclides with K _d of ca. 5 X 10⁴ ml/g, i.e. which are highly associated with the SPM (2 mg/l). The scavenging effect by SPM seemed to be, however, considerable, the settling velocity being estimated at ca. 25 cm/day for particles of the Stoke's diameter of 30 μm.     

Soil-to-Plant Transfer Factors of Stable Elements and Naturally Occurring Radionuclides (1) Upland Field Crops Collected in Japan

In long-term dose assessment models for radioactive waste disposal, an important exposure pathway to humans is via ingestion of contaminated foods. In order to obtain soil-to-plant transfer factors (TFs) of radionuclides under equilibrium conditions, naturally existing elements were measured as analogues of radionuclides. Crops grown in upland fields and associated soil samples were collected from 62 sampling sites throughout Japan. The total concentrations of 52 elements in the crops and 54 elements in the soil samples were measured. The TFs of 40 elements (Li, Na, Mg, Al, Si, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Y, Mo, Cd, Sn, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Pb, Th and U) were calculated on a dry weight basis.

Among all the TF data, K showed the highest TF with a geometric mean (GM) of 2.1, followed by P. The GMs of TFs for rare earth elements, Th and U were on the order of 10^?4. Most of the TF-GMs for green vegetables were higher than GMs of all crops for the elements. The obtained TFs of some elements for green vegetables and potatoes were compared with those in the technical report series-364 (TRS-364) compiled by IAEA in 1994. The TF-GMs were usually lower than the best estimates (expected values) listed in TRS-364; however, the GMs of TF for La and TF for Th observed for potatoes were slightly higher than the expected values.     

Analytical Models for Migration of Radionuclides in Geologic Sorbing Media

In safety evaluation of nuclear waste repository systems, the analysis on migration of radionuclides in geologic media is important. In previous analytical models called Band- Release, Step-Release and Impulse-Release for decay chains, nuclide-specific release rate and time-dependence of release rate can not be taken into consideration. In this paper, two new release models are proposed. In Preferential-Release model, both of nuclide-specific release rate and time-dependence of leach are taken into account. Exponential-Release model is a special case of Preferential-Release model, in which no preferentiality in leach is assumed. The obtained analytical solutions for these new models are applicable even to four or more member decay chains and are as simple as those for the previous models.

As an example of the application of the new models, the discharge rates of the four nuclides in the decay chain of ²³⁸Pu→²³⁴U→ ²³⁰Th→²³⁶Ra→ into a surface water body are calculated as a function of time after the start of leach and path length from the repository. By using the result, heavy hazard due to ²³⁸Pu at short distance and ²²⁶Ra at long distance are also discussed briefly.     

A rapid-detection method for radioactive cesium in the air

We propose a method of rapidly detecting radioactive cesium floating in the air for the purpose of alerting people active in the ‘difficult-to-return zone’ of Fukushima to changes in airborne radioactivity. With this purpose in mind, we set requirement specifications and created a new system concept. The targeted detection limit was 30 Bq/m³ and the mandatory level of measurement time was 48 min with a target level of 12 min, and these periods are 10 times faster than those of conventional air monitors. The system consists of a conventional gamma-spectrometer with a novel shaped shield. The targeted peak region of the measured energy spectrum is analyzed. After the basic design and confirmation of feasibility, we perform some experiments in the normal environment of Yokohama city and the difficult-to-return zone of Fukushima. Using the results, we conducted the design improvement and performance evaluation. As a result, the system performance is found to satisfy requirements. We thus conclude that this system is a promising candidate for rapid detection of airborne radioactivity in the difficult-to-return zone of Fukushima.     

某矿区石煤样品中放射性核素的测定及评价

介绍了某矿区石煤样品的采集、制样和选择适宜的室内分析方法,在实验室质保体系控制质量的条件下,准确测定了放射性核素含量;基于检测结果为该项目辐射环境影响作初步评价,提出了防治污染的措施。