低剂量全身照射在非清髓性干细胞移植中的临床研究

目的 观察非清髓性低剂量全身照射的临床效果和急性毒副作用。方法 2006年1月至2008年1月对27例异基因造血干细胞移植患者采用含有全身照射的非清髓预处理方案:全身照射(TBI)2 Gy,一次完成;受者原发病不同,受者机体状态、年龄、脏器功能以及供受者HAL相合情况等不同,使用的化疗方案也有不同,包括氟达拉宾、环磷酰胺、阿糖胞苷、马法兰等。预防移植物抗宿主病(GVHD)采用:环孢霉素、霉酚酸酯。结果 造血重建情况: 27例均于移植后第4~8天外周血WBC降至(0.05~0.9)×10⁹/L。中性粒细胞计数>0.5×10⁹/L为8~22 d(中位数为10.5 d),血小板计数>30×10⁹/L为11~28 d(中位数为14.5 d)。1、2年生存率为85.2%(23/27)、77.8%(21/27)。发热率65%,10例发生感染。无出血性膀胱炎和肝静脉闭塞症等并发症。急性GVHD 4例(15%), 慢性GVHD 5例(19%)。随访3~22个月21例(77.8%)仍存活。结论 采用低剂量全身照射的非清髓性造血干细胞移植预处理方案简便安全,并发症少,适应证广;全身照射总剂量2 Gy,1次完成的方案是安全有效的,可以达到免疫抑制效果。     

低剂量率裂变中子照射对大鼠外周血淋巴细胞亚群的影响

目的 探讨低剂量率中子长期照射对大鼠外周血细胞亚群的影响。方法 96只雄性大鼠分为对照组和照射组,照射组每天用低剂量率中子²⁵²Cf(吸收剂量率为0.35 mGy/h)照射20.5h,在照射的第14、28、42、56和70天(累积剂量分别为0.1、0.2、0.3、0.4和0.5 Gy)及停止照射后第35天各取8只大鼠,用血细胞计数仪检测大鼠外周血WBC、用流式细胞仪检测外周血CD4⁺CD3⁺、 CD8⁺CD3⁺、CD45RA⁺/CD161α⁺亚群的变化。结果 累积剂量为0.3、0.4及0.5 Gy时WBC明显低于对照组(P<0.05),停止照射后35 d,WBC显著低于对照组(P<0.01);累积剂量为0.1、0.3、0.4、0.5 Gy及停止照射后35 d,外周血CD4⁺CD3^-细胞比例显著高于对照组(P<0.01或<0.05);累积剂量为0.2和0.3 Gy时CD8⁺CD3^-细胞比例显著高于对照组(P<0.05或P<0.01)。而累积剂量为0.1 Gy时的CD4⁺CD3⁺细胞比例及0.1和0.2 Gy时的CD8⁺CD3⁺细胞比例明显高于同一天对照组(P<0.01或<0.05)。另外,低剂量率中子长期照射可使累积剂量为0.2~0.3 Gy的外周血NK细胞(CD161α⁺ CD45RA^-)显著升高,累积剂量为0.1~0.5 Gy及停止照射后35 d照射组的外周血B细胞(CD161α^- CD45RA⁺)比例明显下降。结论 低剂量率裂变中子长期照射可使外周血淋巴细胞TCR基因突变,使大鼠外周血WBC减少,淋巴细胞中B细胞减少,NK细胞细胞比例升高,这种变化在停止照射后一段时间仍可能难以恢复。     

同种异基因胎肝移植治疗急性放射病的临床研究

本文报道4例眙肝细胞移植治疗事故性(例1)或医疗性(例2～4)重度骨髓型急性放射病的临床研究,全身照射剂量:倒l为5.2Gy;浏2～4分别为5.5,5.0和5.0Gy.后3例并用大剂量化疗:环磷醚胺80mg/kg,输入胎肝细胞数2.26～4.1×10³/kg体重(胎肝数l～13个).除1例有局限于皮肤的I级轻篓抗宿主病外,其余无不良反应。提出胎肝细胞移植或输注在事故性照射引起中度以上骨髓型急性放射病,又缺乏HLA相合供者钓情况下不失为一有用的治疗措施。对3例急性白血病也是一个治疗措施,1例已生存近5年,另一例也已3年多。     

低剂量率60Coγ线长期慢性照射和一次急性照射雄性小鼠诱发显性致死突变的研究

每天以2.02、3.84、7.68和13.03拉德γ线慢性照射雄性小白鼠,诱发的显性致死突变率均高于对照组。其中7.68和13.03拉德组的诱发率与累积剂量线性相关,分别为2.19×10^-4/拉德和2.63×10^-4/拉德。以114拉德/分剂量率一次照射小白鼠精子和精细胞的诱发率均与照射剂量呈线性相关,分别为0.75×10^-3/拉德和1.49×10^-3/拉德。慢性照射和急性照射精原细胞诱发的显性致死突变与累积剂量均无相关性。     

细胞因子联合对4.5Gyγ射线照射比格犬造血损伤的治疗作用

目的 观察细胞因子组合对4.5 Gy γ射线照射比格犬造血系统损伤的治疗效果,为极重度骨髓型急性放射病的临床救治提供实验依据。方法 16只比格犬均给予4.5 Gy ⁶⁰Co γ射线全身照射,随机分为照射对照、综合对症和细胞因子3组。细胞因子组动物在综合对症支持治疗的基础上应用rhG-CSF、rhIL-11和rhIL-2联合治疗。2 d检测1次外周血象,分别于照射前4 d,照射后1和45 d收集骨髓和外周血进行造血细胞集落培养,制备胸骨病理切片观察组织形态学改变。结果 照射后各组动物外周血各类细胞数急剧下降,细胞因子联合治疗可提高白细胞最低值(1.04×10⁹/L,而照射对照组和综合对症组分别为0.28×10⁹/L和0.68×10⁹/L),缩短血小板减少持续时间(细胞因子组24 d,综合对症组33 d),使红细胞维持在正常值范围;照射后1 d骨髓及外周血中造血干细胞集落形成率明显下降,照射后45 d 2个治疗组造血干细胞集落数均恢复为照射前水平;照射对照组动物骨髓造血细胞完全消失,细胞因子治疗使得骨髓造血功能完全恢复,与照射前水平比较差异无统计学意义。结论 rhG-CSF、rhIL-11和rhIL-2联合应用可提高极期时外周血白细胞最低值,加速白细胞、血小板和红细胞恢复,促进4.5 Gy γ射线照射犬体内残留造血干/祖细胞的增殖、分化和成熟,从而加速造血功能的重建。rhG-CSF、 rhIL-11和rhIL-2不失为治疗极重度骨髓型急性放射病的有效措施。     

氚辐照生物效应研究中的内剂量估算

为了在氚辐照生物效应研究中对内照射剂量给出比较准确的估算,本文根据小鼠单次和持续给予氚水的代谢实验,讨论了不同给予方式下的内剂量估算,给出了小鼠不同组织或器管的估算结果。单次给予氚水1Bq/g体重时65天内的总剂量,脂肪约8×10^-8Gy,其它组织约20×10^-8Gy。持续给予氚水1Bq/1时的剂量率,脂肪约为0.16×10^-10Gy/d,其它组织平均约0.32×10^-10Gy/d,全身约0.28×10^-10Gy/d。     

贵州省部分矿山放射性水平的评价

目的 调查和评价贵州省铝、锰、锑、磷、汞等部分矿山放射性水平。方法 对矿区氡气、钍气浓度进行累积1年的现场检测;采集矿石、矿山周围土壤进行放射性核素分析;对矿区γ辐射水平进行测量;对矿山渗透水进行总α、总β测量。结果 某铝矿山春、夏两季井下氡浓度水平为626.0～3866 Bq m³,秋、冬两季为38.9～655.0 Bq m³,全年平均值为1374 Bq m³;春、夏两季井下钍浓度水平为626.0～4834 Bq m³,秋、冬两季为40.9～344.0 Bq m³,全年平均值为1221 Bq m³。其余矿山均低于此水平。矿石放射性核素²²⁶Ra为6.9～511.9 Bq/kg、²³²Th为1.4～536.7 Bq/kg、⁴⁰K为<17.5～433.7 Bq/kg。γ外照射最高的为铝矿,平均值(87.0±8.1)×10^-8 Gy/h,最低的为锑矿,平均值(6.0±1.9)×10^-8 Gy/h。矿山井下水总α为小于探测下限～17.5(×10^-2Bq/L),总β为小于探测下限～37.4(×10^-2Bq/L)。结论 此次调查的部分矿山,大多采用机械和自然相结合的通风方式,通风情况较好。但铝矿井下的氡、钍浓度水平明显高于井外,全年平均值分别是井外的78倍和15倍;铝矿的γ外照射平均值(87.0±8.1)×10^-8 Gy/h,也明显高于贵州省γ天然辐射平均值(13.3×10^-8 Gy/h)。这将对该矿的矿工增加一定的附加剂量。     

中国环境天然贯穿辐射水平与评价

本文报告了我国天然贯穿辐射累积剂量调查结果。调查所用环境剂量计为国产ETLD一80型热释光环境剂量计。调查结果表明,我国室外地球γ 辐射空气吸收剂量率人口加权平均值为6.7×10^-8Gy·h^-1,室内为3.9×10^-8Gy、h^-1,室外宇宙辐射电离成分宅气吸收剂量率人口托权均值为3.3×10^-8Gy·h^-1室内为2.9×10^-8Gy·h^-1.地球γ 辐射所致居民人均年有效剂量当量为519μSv; 宇宙辐射电离成分所致居民人均年有效剂量当量为26lμSv.     

造血干细胞移植中预先全身照射对全身及造血系统的影响及并发症治疗

目的 探讨全身照射联合高剂量化疗对造血干细胞移植患者全身和造血系统影响的特点和治疗,为急性放射病的诊治提供临床经验。方法 回顾分析64例接受造血干细胞移植患者,系统观察急性照射及大剂量化疗后患者血液学改变及临床不良反应,并分析其骨髓重建特点。结果 移植相关病死率3.12%。移植后随访9～72个月 (中位随访时间26个月)。1、3、5年生存率分别为(95.8±3.3)%, (89.8±4.7)%和(81.7±6.9)%。全身照射联合高剂量化疗后,所有患者均出现了血液学不良反应,以白细胞及血小板下降最为明显,白细胞总数最低值为(0.18±0.13) ×10⁹个/L,血小板最低值为(14.48±8.85)×10⁹个/L;在造血干细胞支持及粒细胞集落刺激因子(G-CSF)应用后,均可恢复。此外患者不同程度出现消化道反应、感染、肝功能受损及出血等不良反应,经相关治疗后好转。结论以TBI联合高剂量化疗为预处理,随后进行造血干细胞移植,患者恶性血液系统疾病治疗效果好,并且其临床情况在一定程度上模拟了急性放射病的临床过程,为急性放射病的救治提供了一定的临床经验。     

小鼠放射性肠炎模型的建立

目的 建立小鼠放射性肠炎模型。方法雌性BALB/c小鼠84只,随机分为对照组(24只)、6 Gy组(28只)及10 Gy组(32只),⁶⁰Co γ射线对小鼠腹部一次性照射,在照射后3、7、14和21 d检测血象及肝、肾功能,并取肠道组织做病理及一氧化氮(NO)检测。结果照射后3、7 d,6 Gy及10 Gy组WBC、PLT均较对照组降低;10 Gy组肝功能异常;10 Gy组照射后3 d肠道组织NO水平降低;照射后3、7 d,2个照射组小肠绒毛高度降低,隐窝深度变浅、数目减少,隐窝腔变大,均出现放射性肠炎改变,10 Gy组死亡较多,6 Gy组更能模拟临床放射性肠炎,为研究提供模型。结论⁶⁰Co 射线一次性腹部照射建立小鼠放射性肠炎模型,6 Gy照射剂量更为合适。     

人体中的镭-226、镭-228、钋-210、铅-210

本文报道了广东阳江高本底地区6名、对照地区8名人尸体的骨²²⁶Ra、²²⁶Ra的浓度以及部分居民内脏器官中。²¹⁰Po、²¹⁰Pb的浓度。结果轰明阳江高本底地区和对照地区居民骨镭-226、镭-228的浓度分别为29.9pCi/kg, 26.9pCi/kgl 8.7pCi/kg, 8.2pCi/kg.由此估算出阳江高本底地区屠民骨中²²⁶Ra、²²⁸Ra的负薄璧及对骨衬、骨髓所产生的剂量当量分别为对照地区民民的3.4倍, 3.3倍。两地区居民内脏器官中^{210Po、210Pb的测定分析铡数较少但仍看出, 高本底地区均明显高于对照地区.}     

Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent

The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of (90)Y via a (90)Sr/(90)Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, (90)Y is repeatedly isolated from an 11.8-GBq (320 mCi) (90)Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for (90)Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of (90)Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and (90)Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of (90)Y.     

Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide synovectomy

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.     

Rapid determination of Sr impurities in freshly “generator eluted” Y for radiopharmaceutical preparation

⁹⁰Y is one of the most useful radionuclides for radioimmunotherapeutic applications and has a half-life (t_1/2=64.14 h) suitable for most therapeutic applications, beta particles of high energy and decays to a stable daughter. It is significant that ⁹⁰Y is available conveniently and inexpensively from a radionuclide “generator” by decay of its parent, ⁹⁰Sr. Nevertheless, current and planned clinical applications with [⁹⁰Y] labelled compounds employ activity levels that cannot be readily obtained from an in-house generator, but from commercial sources. We have evaluated Eichrom's Sr-resin, either as an “in-house” generator or as a fast QC method for analysis of ⁹⁰Y solutions.In particular, for the development as a generator, we investigated the percentage of the radio-Sr in the first 8 M HNO₃ eluate: in this fraction the concentration of ⁹⁰Sr must be smaller than 10⁻⁵% (recommendations of the International Commission on Radiological Protection). For evaluation as a rapid QC method, we analyzed the concentration of ⁹⁰Y in all the fractions containing “only” radio-Sr: ⁹⁰Y should not be present in these eluates. After the collection of β⁻ and γ spectra and analysis of them, we concluded that commercial Sr-resin minicolumn cannot give us the results expected; we developed an in-house system loaded with 4 mL of Sr-resin which gave better results as a generator and a rapid QC method.     

Radiobiological Issues in the Anomalous Enhanced Effect of Low-dose-rate Fission-spectrum Neutrons: Reply to Letter to the Editor by G. W. Barendsen

Summary

The influence of diet or its ingredients on ¹⁴¹Ce absorption and retention was investigated in six-day-old rats. Animals were fed over 8 h with cow's milk, rat diet or a mixture of rat diet ingredients (fish meal, sunfiower meal, alfalfa, cane molasses and premix) labelled with ¹⁴¹Ce. Whole-body radioactivity was determined in a double crystal scintillation counter every 24 h over a six-day period. Gut, liver, kidney and femur retention and cerium distribution in the gut was determined at the end of the experiment. Compared to milk diet, administration of rat diet or ingredients caused respectively 3 and 7·5 times lower whole body retention. Carcass retention was reduced by rat diet or ingredients 2–3 times and intestinal retention 3 and 8 times respectively. Irrespective of the dietary treatment the main site of cerium intestinal retention was the ileum. Our present results indicate that some compounds of rat diet might be considered as a means of reducing cerium absorption and intestinal retention in the very young.     

226Ra 228Ra 210Pb和210Po在水生生物及食物链中转移规律的探讨

目的 为了解天然放射性核素²²⁶Ra、²²⁸Ra、²¹⁰Pb与²¹⁰Po在水生物及食物链中转移和蓄积情况。方法 定点采集养殖水产品及栖息环境中水与底质沉积物, 按不同的实验需要, 每个鲜样分别剥取肉, 骨(壳),鳞片和胃肠。烹饪样品, 洗净、称重、清炖, 熟后分离出骨(壳),余为食物。样品分别测定²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po含量。数据按统计学要求处理, 配对数据, 作了配对显着性检验。结果 ²²⁶Ra、²²⁸Ra和²¹⁰Pb主要沉积于骨(壳)中, 浓集系数为10²～10³,肉中为10⁰～10².²¹⁰Po主要蓄积在水生物胃肠中, 浓集系数在10²～10⁴,鱼类胃肠与贝类肉中可达10⁴.水产食品烹饪加工过程²²⁶Ra、²²⁸Ra和²¹⁰Pb在食物链中转移不明显, 经配对显着性检验, 差异无显着性(P0.05);然而210Po在淡水鱼类和虾类中转移是明显的, 肉配对检验有非常显着性差别(P<0.01).结论水生物对²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po有很强浓集能力。     

Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

In an attempt to visualize folate receptors that overexpress on many cancers, [¹⁸F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([¹⁸F]-1, [¹⁸F]-2-folates and [¹⁸F]-8, [¹⁸F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [¹⁸F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [¹⁸F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [¹⁸F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [¹⁸F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.     

Scintigraphic findings of MALT lymphoma of the thyroid

Mucosa-associated lymphoid tissue (MALT) lymphoma has been established as a distinct entity among non-Hodgkin's lymphomas, and the most common primary site is the stomach. We describe scintigraphic findings in a patient with MALT lymphoma of the thyroid. A 71-year-old woman with Hashimoto's thyroiditis suffered from rapid cervical swelling, and ultrasonography and CT revealed a thyroid nodule. The nodule showed accumulation of 99mTc pertechnetate comparable to the surrounding thyroid tissue, mimicking a benign nodule. Both 67Ga and 201Tl imaging visualized the lesion as an increased uptake area. After radiotherapy, abnormally increased uptake disappeared on 67Ga images, which predicted a favorable outcome. MALT lymphoma of the thyroid may be visualized as a warm nodule on 99mTc pertechnetate scintigraphy.     

The role of I-131-MIBG in the diagnosis and therapy of carcinoids

The successful use of ¹³¹I-MIBG for the diagnosis and treatment of pheochromocytoma and neuroblastoma has led to its application in patients with carcinoid, another neural crest tumor. The present report describes the scintigraphic findings, in correlation with clinical and biochemical parameters, in 20 patients with histologically proven carcinoids. ¹³¹I-MIBG total body scintigraphy was positive in 12 and equivocal in 1 of 19 patients with metastases. The necessity of delayed imaging and the possible advantage of single photon emission tomography for the detection of this tumor are emphasized. The results of ¹³¹I-MIBG treatment in five patients with progressive carcinoid metastases are discussed. It is concluded that ¹³¹I-MIBG has a role in the work up of patients with proven carcinoid and can be used for palliative treatment of this tumor.     

Development of a modular system for the synthesis of PET [C]labelled radiopharmaceuticals

[¹¹C]labelled radiopharmaceuticals as N-[¹¹C]methyl-choline ([¹¹C]choline), l-(S-methyl-[¹¹C])methionine ([¹¹C]methionine) and [¹¹C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [¹¹C]choline, [¹¹C]methionine and [¹¹C]acetate using components that account for straightforward scaling up and upgrades.