211At及131I标记尼妥珠单抗的荷瘤小鼠体内治疗研究

以靶向表皮生长因子受体(EGFR)的尼妥株单抗(nimotuzumab)为载体,开展²¹¹At和¹³¹I一步法标记流程的建立和对荷U87MG胶质瘤裸鼠的初步治疗研究。结果表明,标记率约95%,在磷酸缓冲液（PBS）和10%胎牛血清（FBS）中能保持一定稳定性;瘤内注射24 h后,药物在肿瘤的放射性摄取率仍然能保持在（28.2±4.7）%ID·g^-1;¹³¹I/²¹¹At-ATE-nimotuzumab均可对U87MG实体瘤的生长产生明显的抑制作用,且呈剂量相关性;整个治疗过程中,药物对荷瘤鼠体重无明显影响并且有效地延长了生存时间;相较而言,20 μCi的²¹¹At-ATE-nimotuzumab治疗组荷瘤小鼠中位生存时间长于200 μCi ¹³¹I-ATE-nimotuzumab治疗组荷瘤小鼠的中位生存期,分别为35 d和31.6 d。该工作进一步确定了α核素²¹¹At在放射性靶向治疗研究中的潜力,为相关药物的临床前基础研究提供了重要参考。     

~(131)I标记新型小分子肽VP2

本文通过双功能偶联剂5-(三正丁基锡)-3-吡啶甲酸-N-琥珀酰亚胺酯(SPC)将131I标记到小分子融合多肽VP2上,研究了131I标记多肽VP2的体内外稳定性及在正常小鼠体内的代谢与分布。结果表明,该标记药物室温下放置48h后放化纯度仍可达97%,其在小鼠体内可通过胃肠道快速代谢,在甲状腺的摄取较低。用间接标记法得到的131I-SPC-VP2在体内外有良好的稳定性。     

碘标记毒死蜱及其在小鼠体内的生物分布

为探讨¹³¹I标记毒死蜱（Chlorpyrifos, CPF）在小鼠体内的分布特点,采用Iodogen法对CPF进行¹³¹I标记,KM小鼠尾静脉注射¹³¹I-CPF（185 kBq/只,n=5）,分别于注射后5、10、30、60、120、240、1440 min取各脏器,计算每克组织摄取注射剂量的百分率（%ID/g）。结果显示,¹³¹I-CPF标记率达93.5%,放化纯度为96.9%,¹³¹I-CPF在小鼠体内广泛分布,主要经肺、胃、小肠、大肠、肌肉和颌下腺吸收,其放射性摄取率在注药后 10 min 时达高峰,分别为37.12%ID/g、6.18%ID/g、8.12%ID/g、8.15%ID/g、7.04%ID/g和7.02%ID/g;经肝和肾进行代谢,其放射性摄取率在5 min时分别为4.34%ID/g和8.50%ID/g, 4 h为0.22%ID/g和 0.69%ID/g。血液中放射性清除较快,放射性摄取率在注入后5 min时为37.27%ID/g,4 h为1.35%ID/g。碘标记CPF体外稳定,体内主要经肺和消化道吸收,肝、肾代谢,可用于进一步的微量示踪研究。     

Radioiodine-Labeling of Chlorpyrifos and Its Biodistribution in Mice

To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with¹³¹I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq¹³¹I-Chlorpyrifos/mouse, n=5), the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g) was calculated for each sample. The labeling yield of ¹³¹I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP) was 96.9%. Biodistribution in mice demonstrated that¹³¹I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition,¹³¹I-Chlorpyrifos was cleared out from blood quickly, and the uptake of¹³¹I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, ¹³¹I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.     

海水中~(131)I的快速检测技术

日本福岛核事故发生以后,对海洋环境中关键放射性核素的快速检测技术提出了更高的要求。人工放射性核素~(131)I在核反应裂变产物中活度相对较高且半衰期短,是用来快速评价核污染的关键性核素之一。本工作从亚铁氰化钾、硝酸铜及硝酸银为原料出发,制备出亚铁氰化铜和亚铁氰化银混合(CuFC/AgFC)吸附材料并分散于聚丙烯纤维富集柱上,来实现水环境中~(131)I现场快速富集。通过室内模拟实验发现:在流速为6.25L/min,~(131)I在海水中I~-初始浓度为24μmol/L时,单次吸附效率即可达到50%以上;而当海水中I~-初始浓度为4μmol/L时,一定体积的海水在连续循环8次后(CuFC/AgFC)聚丙烯纤维富集柱吸附效率达到100%。本方法制源时间约40min,测样时间约12~24h,故最快可在30h内完成海水中~(131)I的分析。本方法的检测限与分析周期均低于目前GB/T 13272-1991水中~(131)I的分析标准,极大地提高了~(131)I的分析时间。除此之外,该法可以同时分析海水中的~(137) Cs(~(134) Cs),有望作为淡水和近岸环境中常规监测和应急时对关键核素~(131)I和~(137) Cs(~(134) Cs)进行快速测定的备选方法之一。     

纤维蛋白显像剂131I-YSSCREKA肽的制备及对早期血栓定位的研究

合成了一种可特异性结合纤维蛋白-纤维连接蛋白的早期血栓显像剂¹³¹I-YSSCREKA肽（酪氨酸-（D）丝氨酸-（D）丝氨酸-半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸），对其标记、SPECT显像及初步生物学性能进行研究。结果表明：YSSCREKA八肽在室温下通过氯胺-T法反应5 min的标记率为(77.2±1.1)%（n=3），放射化学纯度为(90.0±3.1)%（n=3），体外稳定性较好。新西兰家兔SPECT显像显示在¹³¹I-YSSCREKA肽注射后20 h血栓能较清晰地显像，血栓/血放射性比值为1.36。SD大鼠生物分布实验显示：20 h ¹³¹I-YSSCREKA肽在血栓中的摄取率为(0.19±0.06)ID%/g（n=5），血栓/肌肉及血栓/血放射性比值分别为3.80和1.90。¹³¹I-YSSCREKA肽有可能作为早期血栓的显像剂，但其在血栓中的摄取率有待于进一步提高。     

Radioiodine-labeling of EGCG and Its Biodistribution in Mice

To establish the ¹²⁵I-EGCGlabeling method and investigate the biodistribution of ¹²⁵I-EGCG inmice, ¹²⁵I-EGCG was prepared by Iodogen solid labeling method, andwere isolated and purified by Sephadex-G25 agarose, The labeling yield andradiochemical purity of ¹²⁵I-EGCG was analyzed by polymide TLC. Thelabeling yield of ¹²⁵I-EGCG was 89.4% and its radiochemicalpurity(RCP) were 96.4%. The Biodistribution of ¹²⁵I-EGCG in mice wasmeasured at different times after caudal vein injection with 185 kBq for eachmice. The biodistribution in mice demonstrated that ¹²⁵I-EGCG wasdistributed into broad organs and tissuuues, especially in the Stomach, Smallintestine and Submaxillay gland, and the biggest uptake of ¹²⁵I-EGCGin there organs was 15.92、5.83and 11.56 %ID·g^-1respectively at 15 min post injection. In addition, ¹²⁵I-EGCG wascleared out from blood guickly, and theuptake of ¹³¹I-EGCG in blood was 11.95 at 5 min, anddecreased to 1.25 at 4 h post injection. Therefore, ¹²⁵I-EGCG wasstable and it was metabolized mainly in Stomach, Small intestine, Submaxillaygland, worthy of further investigation to trace the compound in vivo and invitro.     

干馏法从铀的裂变产物中分离131I

¹³¹I是一种重要的医用放射性同位素,但因湿法分离技术上的缺陷,使得从铀裂变产物中获取¹³¹I的工艺具有环境污染严重、提取效率低的缺点。因铀裂变产物中¹³¹I的产额较高,为拓展¹³¹I的获取途径,提高铀裂变产物的利用效率,开展铀裂变产物中¹³¹I分离的新工艺研究十分必要。与传统湿法分离工艺不同,本工作采用了干馏法进行铀裂变产物中¹³¹I的分离。为了得到高的¹³¹I分离效率,将分离过程分为低温粉化、高温干馏和中低温保温三个阶段,并研究高温干馏阶段温度对131I分离效率的影响。实验发现：当干馏温度高于950 ℃时,¹³¹I的分离效率≥98%。此外,研究结果还表明,在该干馏温度下,碘和¹⁰³Ru 均可挥发出铀靶片,但产物收集液中却仅含有碘。为了解释这一现象,对碘的分离过程进行分析,结合实验结果和理论计算,推测挥发物中碘和¹⁰³Ru分离的原因为：¹⁰³Ru与氧反应生成挥发性RuO₄,从铀的裂变产物挥发出;因加热管内温度较高,RuO₄在迁移过程中发生了分解,生成RuO₂沉积在加热管内部。因此,利用干馏法从铀的裂变产物中分离¹³¹I时,为了得到放化纯度高的碘产品,不仅要合理规划分离过程,还需科学设计加热管的长度。     

中国核动力院外围空气中7Be、40K、60Co、131I、137Cs分布特征及所致公众年有效剂量评价

基于2015—2017年中国核动力院外围空气中⁷Be、⁴⁰K、⁶⁰Co、¹³¹I、¹³⁷Cs监督性监测数据,对综合楼、南坝工会和木城水厂监测点附近居民组三种途径的有效剂量进行了粗略估算。结果表明:随距核设施距离增加,⁶⁰Co、¹³¹I、¹³⁷Cs平均年摄入量和所致年有效剂量减小;综合楼附近居民组中成人、青少年、儿童、幼儿、婴儿经吸入⁷Be、⁴⁰K、⁶⁰Co、¹³¹I、¹³⁷Cs平均年摄入量分别为29.25、26.48、20.16、11.49、6.79 Bq/a;综合楼附近居民组中青少年、儿童、成人、幼儿、婴儿,经吸入、浸没和地面沉积途径⁶⁰Co、¹³¹I、¹³⁷Cs所致年有效剂量分别为133.58、130.98、128.61、120.20、118.61 nSv/a,⁶⁰Co所致剂量分数达到95.6%,其次是¹³⁷Cs;地面沉积途径所致剂量分数达到54%,其次是吸入;综合楼附近居民组中青少年组成员⁶⁰Co、¹³¹I、¹³⁷Cs所致有效剂量最大为133.58 nSv/a,但此有效剂量也仅占评价剂量目标值(0.25 mSv)的1‰以下。由此可以得出,核基地核设施正常运行工况下,⁶⁰Co、¹³¹I、¹³⁷Cs对核基地外围空气的影响很小。     

核医学含碘废水排放管理的一些问题

介绍ICRP第94号出版物中对含¹³¹I药物使用的辐射防护和环境影响相关内容,比较国内现有标准对核医学应用含碘废水排放的规定及含碘废水排放存在的问题,讨论了含碘废水的分析方法,分析计算实现达标排放所需衰变池的大小,并给出了含碘废水排放管理的建议。     

Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes

In continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the brain sections of AD model mice specifically, in vitro binding assay further confirmed that they displayed high binding affinities to Aβ aggregates (K_i=2.33 nM and 0.88 nM). One radio-iodinated probe, ¹²⁵I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemical yield and purity (>99%). Moreover, the¹²⁵I-labeling compound displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background, and the specific labeling could be confirmed by thioflavin-S staining. In vivo biodistribution in normal mice indicated that the¹²⁵I labeling compound exhibited low initial brain uptake (1.19%ID/g at 2 min) and rapid clearance. These preliminary results suggest that¹²⁵I labeling compound may serve as novel Aβ imaging probe, although further modifications are needed to improve initial brain uptake.     

靶向整合素α_vβ_3受体的新型RGDyC-PEG-PAMAM纳米探针的设计制备、~(131)I标记及其质量控制

本研究以具有优良生物学性能的聚酰胺-胺树状大分子(PAMAM)为纳米载体,将具有肿瘤靶向性的精氨酸-甘氨酸-天冬氨酸(RGD)与纳米载体相连,并通过放射性核素~(131)I进行标记,对标记物的体内外药效学性质进行评价,探讨将其应用于肿瘤特异显像和靶向治疗的可能性。从多肽化学修饰法角度设计精氨酸-甘氨酸-天冬氨酸-酪氨酸-半胱氨酸(RGDyC),利用点击化学法引入双功能基团PEG(NHS-PEG-MAL),采用"一锅两步"法制备RGDyC-PEG-PAMAM纳米复合物,通过核磁共振和紫外光谱进行表征确定产物,并检测纳米粒径分布和电位,用透射电镜(TEM)观察其形态大小及分布;进一步采用氯胺T法进行~(131)I标记,并测定标记率、标记物的稳定性及脂水分配系数。所设计的RGDyC-PEG-PAMAM纳米复合物制备产率为62.09%,~(131)I对其标记率为94.68%~98.87%,标记物在体外72h后放化纯大于80%,脂水分配系数lg P(正辛醇/水)为-1.59±0.09。所设计的RGDyC-PEG-PAMAM可采用氯胺T法成功完成~(131)I标记,制备与标记过程高效、简捷,标记物~(131)I-RGDyC-PEG-PAMAM具有良好稳定性和较高亲水性,成药性良好,为后期进一步考察体外肿瘤细胞摄取与生长抑制、评估人癌裸鼠异种移植瘤模型治疗及肿瘤显像等体内外药效学研究奠定了基础,~(131)I-RGDyC-PEG-PAMAM有可能作为一个新型SPECT探针应用于肿瘤特异显像与靶向治疗。     

Radio-HPLC分析方法测定治疗用碘［131I］化钠胶囊的放射化学纯度

为建立放射性-高效液相色谱分析方法测定治疗用碘［¹³¹I］化钠胶囊放射化学纯度,采用十八烷基硅烷键合硅胶填充的色谱柱（4.6 mm×250 mm×5 μm）,以5.85 g/L氯化钠溶液（加入0.65 mL正辛胺并用稀磷酸调pH至7.0）-乙腈（V∶V=20∶1）为流动相,串联紫外-可见分光检测器（检测波长为220 nm）与放射性流量检测器,柱温为25 ℃,运行40 min,1.5 mL/min进行等度淋洗,可有效地将主峰碘［¹³¹I］化物与放射性化学杂质碘［¹³¹I］酸根进行分离,碘［¹³¹I］化物和碘［¹³¹I］酸根分别在0.19~92.50 GBq/L和0.15~4.81 GBq/L活度浓度范围内线性关系良好,相关系数r分别为0.993和0.997,碘［131I］化物和碘［131I］酸根的检测限分别为3.21×10^-2 GBq/L和4.74×10^-2 GBq/L,定量限分别为9.63×10^-2 GBq/L和7.91×10^-2 GBq/L,回收率为70.0%～125.0%,耐用性和精密度良好。该法适用于治疗用碘［¹³¹I］化钠胶囊的放射化学纯度测定,为制定该类药物的质量控制标准提供了技术参考。     

碘［131I］原料液瓶中放射性废气收集装置的研制和应用

碘［¹³¹I］放射性药品生产过程中放射性原料液瓶开启时,瓶内积存的放射性废气集中释放,易造成放射性废气污染,以至排放超标。为实现放射性废气的半自动收集与暂存,本研究结合实际生产条件,克服热室尺寸受限、耐辐照、可操作性及通用性等难点,研制一套碘［¹³¹I］原料液瓶中放射性废气收集装置,并对收集的放射性废气进行测量和分析。结果表明,装置运行稳定可靠;通过收集并测量22批次的¹³¹I废气放射活度,表明收集量与环境温度存在一定相关性;使用三个收集瓶可充分收集储存。碘［¹³¹I］原料液瓶中放射性废气收集装置可有效收集碘［¹³¹I］原料液瓶开启过程中集中释放的放射性废气,降低对操作人员和环境的辐射影响。以上结果对其他碘［¹³¹I］放射性药品生产机构控制碘［¹³¹I］排放有一定借鉴意义。     

131 Ⅰ治疗分化型甲状腺癌的辐射防护

分化型甲状腺癌(DTC)患者甲状腺全切或近全切术后常需要对患者行¹³¹I治疗,¹³¹I单次治疗剂量超过400 MBq时,需住院隔离。随着DTC患者的不断增加,¹³¹I应用越来越广泛,应用量越来越大,辐射防护问题受到人们的广泛关注。本文从病房环境防护、患者自身防护、医护人员防护及周围人群防护等几方面介绍了¹³¹I治疗后患者住院期间及出院后应该采取的防护措施及应注意的一些事项,可以更好地保护患者、医护人员及公众的健康。     

分化型甲状腺癌患者行131I治疗辐射防护的知信行现状调查

为了解分化型甲状腺癌患者¹³¹I治疗辐射防护知信行现状及其相关影响因素,我们采用自行设计的辐射防护知信行问卷对某三甲医院核医学科2018年3—6月期间行¹³¹I治疗的330名甲状腺癌患者进行现场调查。结果提示,分化型甲状腺癌患者¹³¹I治疗辐射防护知识、态度、行为百分制平均得分分别为(58±17.88)分、(90.28±7.48)分、(72.13±7.83)分,三者两两正相关,学历是影响患者辐射防护知识水平的主要因素。甲状腺癌患者¹³¹I治疗辐射防护态度积极,但防护知识水平和行为不足,应注重出院后的防护措施指导,并重点关注低学历患者。     

便携式γ谱仪对137Cs、131I液样探测效率的刻度

便携式γ谱仪主要用于主冷却剂水样中典型核素的现场辅助识别及其活度浓度的测量分析。为确定典型核素特征峰净面积和水样中该核素活度浓度的关系,必须进行源峰效率刻度。本文通过测量¹³³Ba、¹³⁷Cs、⁶⁰Co 3种核素的混合溶液得到效率刻度曲线,然后对不同活度浓度的¹³⁷Cs标准溶液、¹³¹I标准模拟溶液进行测量。结果表明,谱仪均能正确识别¹³⁷Cs、¹³¹I核素,活度浓度测量的相对误差均<10%,初步满足元件破损监测精度和灵敏度的需求。     

Modeling the activity and scaling factor of I in the primary coolant and CVCS resin of operating PWR

To estimate the activity of ¹²⁹I at the primary coolant and chemical and volume control system (CVCS) resin in Korean pressurized water reactor (PWR) plants, a theoretical methodology was developed on the basis of an existing model of primary coolant activity and new model of CVCS resin activity. In order to reflect the difference between ¹²⁹I and ¹³⁷Cs, the different power-related diffusivities in the defective fuel were derived, and the variable removal efficiency of the CVCS resin for ¹³⁷Cs was applied as a function of the coolant activity ratio of ¹³¹I/¹³⁷Cs. The current computational method was validated by using the measured coolant activities of ¹³⁷Cs, and the results show better agreement than a previously suggested parameter correlation method between ¹²⁹I and ¹³⁷Cs. There was also reasonable agreement in a comparison of the results of the test resin columns of the coolant from the PWR plants of other countries. It was shown that the ratio of the effective removal efficiency of ¹²⁹I and ¹³⁷Cs in the CVCS resin linearly influences the activity ratio of ¹²⁹I/¹³⁷Cs in the coolant, but on the other hand, its influence on the activity ratio in the CVCS resin is relatively less sensitive compared with that in the coolant.     

Preparation and Preliminary Biodistribution of No-Carrier-Added Meta［*I］ iodobenzylguanidine

No-carrier-added meta-［*I］iodobenzylguanidine((n.c.a.)［^123/131I］MIBG) has been considered to be promising diagnostic agents for oncology and cardiology, or as targeted radiotherapeutics for neuroendocrine tumors. The synthesis of a fluorous supported precursor for the purification without HPLC of n.c.a.［*I］MIBG was presented and its structure was determined. The precursor was labeled with radioactive iodine and the preliminary biodistribution of n.c.a.［*I］MIBG was studied. The uptake of n.c.a.［¹²⁵I］MIBG were significantly higher than that of c.a.［¹²⁵I］MIBG in heart, spleen, lung and adrenals. This facile preparation method of n.c.a.［*I］MIBG would allow its wider application in clinic.     

临港工业区建设对核电厂液态流出物稀释扩散的影响

临港工业区建设会导致核电厂取排水口局部潮流场发生变化,影响液态流出物稀释与扩散。以中国北部湾的廉江港为例,采用二维数值模拟计算核电厂2台机组投入运行后,考虑和不考虑临港工业区两种情况下夏季中潮¹³¹I和⁶⁰Co在取排水口附近海域的浓度分布和时空变化。结果表明:临港工业区建设前,¹³¹I和⁶⁰Co主要随潮流运动,¹³¹I和⁶⁰Co稀释10倍的浓度平均值包络面积分别为0.9×10^-3km²和1.2×10^-3km²,高浓度区主要分布于排水口所在的安铺湾。临港工业区建设后,潮流场仅在工业区附近发生变化,变化幅度工业区东侧明显大于西侧,并在东侧形成回流区,挑流作用使附近水域的流动减弱,贴近工业区受影响最大,流速、流向均有较明显的改变。¹³¹I和⁶⁰Co稀释10倍的浓度平均值包络面积分别为1.0×10^-3km