妊娠和泌乳对147Pm在小鼠体内代谢的影响

分别经尾静脉给对照, 妊娠和泌乳BALB/c小鼠注射1.85×10⁴Bq/克体重¹⁴⁷Pm(NO₃)₃溶液, 于注射后不同时间分批活杀动物, 以便确定¹⁴⁷Pm的分布和滞留。结果表明, 3组动物体内¹⁴⁷Pm代谢存在着差异。尽管3组动物肝脏初始摄入¹⁴⁷Pm的量均为60%左右, 但是, 妊娠和泌乳组动物肝脏¹⁴⁷Pm生物半排出期比对照组动物显着延长。     

大鼠体内147Pm剂量模型的初步探讨

本文报道了大鼠体内及主要沉积器官¹⁴⁷Pm代谢模式和内照射剂量估算模型。并根据文中报道的剂量模型,估算出静脉内或肺区间内直接注入3.7×10⁴Bq/g体重¹⁴⁷Pm后不同对间主要器官所受到的剂量。     

体内摄人147Pm时诱发放射遗传毒理效应研究

本文研究了机体摄八不周量的¹⁴⁷Pm时诱发的骨髓细胞染色体畸变、姐妹染色单体互换(SCE)频率和微核率的变化过程.实验结果发现¹⁴⁷Pm嚣发的骨髓细胞染色体畸变以染色单体型蹄变为主,且随着¹⁴⁷Pm撮入量的增加,染邑体琦变也相应增多,并可出现染色体断片和易位．研究表明,骨髓细胞染色体畸变率与¹⁴⁷Pm摄人量之同呈半对致直线效应关系,拟合的半对数回归方程式为:Y=-4．403+1．435LnX．同时电观察到骨髓畸变细胞与¹⁴⁷Pm的摄八量之间亦呈线性关系．¹⁴⁷Pm内污染后．诱发骨髓细胞SCE须率和徽核阳性率明显升高.且随着¹⁴⁷Pm摄入量的增加微核率也有所增加.     

147Pm对机体损伤效应的初步观察

选尾体重为100～130克的雄性大白鼠,尾静脉注入不同放射性活度¹⁴⁷Pm硝酸溶液(pH3.5),以外周血液淋巴细胞微核出现率和血清谷丙转氨酶活力变化作为指标,观察¹⁴⁷Pm对机体的损伤效应.结果表明.外周血液淋巴细胞微核出现率对¹⁴⁷Pm辐射较为敏感.其明显升高的下限注入活度为0.05μCi/g.蜂值出现在内污染后6小时.而且在一定放射性活度范国内,微核出现率与¹⁴⁷Pm内污染活度呈线性关系.以血清谷丙转氨酶活力作为指标.在外周血液淋巴细胞微核出现事明显升高的同时,未观察到¹⁴⁷Pm对肝脏有明显的损伤.     

不同辐射体核素体内滞留特性诱发体细胞突变效应比较研究

由子霞校裂片巾不同辐射体核素¹⁴⁷Pm、¹⁵²Eu或¹⁷⁰Tm被机体摄入后滞留的差异．这些稀土族放射性核素诱发对机体骨髓细胞染色体畸变和微核形成的程度．可随着骨组织累积吸收剂量的增加而增升．而这些不同辐射体核素诱发骨髓细胞染色体畸变的类型均以染色单体型畸变为主, 同时也诱发染色体断裂和易位．实验还观察到内污染¹⁴⁷Pm、¹⁵²Eu或¹⁷⁰Tm时, 可在一个细胞中诱发有多个畸变发生, 这表明不均匀辐照可改变畸变分布．而比较形成多畸变细胞和PCE微核率的程度依次为¹⁴⁷Pm>¹⁵²Eu>¹⁷⁰Tm。     

147Pm照射对人白血病HL-60细胞bc-l2和bax基因表达的研究

目的 研究了¹⁴⁷Pm照射对人白血病HL60细胞bcl-2和bax基因表达作用。方法 运用免疫组织化学技术探讨147Pm对HL-60细胞bcl-2/bax的蛋白表达, 以及RNA分子杂交技术探讨¹⁴⁷Pm对HL-60细胞bcl-2mRNA的转录水平表达。结果 发现对照HL-60细胞中bcl-2蛋白呈高度表达, 为88%;在¹⁴⁷Pm照射下, 可下调至53%.bax在对照细胞中的表达很低;¹⁴⁷Pm作用后, 未见明显改变。而受¹⁴⁷Pm照射后, 可使HL-60细胞中bcl2mRNA表达呈明显下调, 并随受照射时间的延长, 下调作用更加显着。结论 ¹⁴⁷Pm诱发人白血病HL-60细胞的凋亡作用, 与其下调凋亡相关基因bcl-2的表达相关联。     

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。     

放射性碘对大鼠致癌效应的研究

对雄性Wisiaf大鼠腹腔1次注射碘-13l, 注入活度分别为0.59×10⁴Bq,2.37×10⁴Bq, 4.34×10⁴Bq, 8.23×10⁴Bq, 碘-125注入活度分别为3.7×10⁴Bq, 7.4×10⁴Bq, 14.8×10⁴Bq, 22.2×10⁴Bq.碘-131诱发肿痛实际注入活度在2.37×10⁴Bq以下,碘-125的为7.4×10⁴以下.诱发的肿瘤以甲状腺肿瘤为主,其次为垂体肿瘤.     

黑龙江省食品和水中天然放射性水平及对居民所致内剂量估算

本文介绍了黑龙江省食品和水中的天然放射性比活度及其对居民所致内照射剂量。测定了23种食品、自来水井水和松花江水中的放射性核素的比活度,²³⁸U、²³⁴U、²³²Th、²²⁶Pa及⁴⁰K、的平均比活度分别是:植物性食品为3.6×10^-2Bq/kg、3.6×10^-2Bq/kg、1.5×10^-2Bq/kg、9.6×10^-2Bq/kg和86Bq/kg;动物性食品为2.6×10^-2Bq/kg、2.6×10^-2Bq/kg、1.0×10^-2Bq/kg、4.6×10^-2Bq/kg、65Bq/kg;饮用水为2.4×10^-2Bq/L、2.4×10^-2Bq/L、2.0×10^-4Bq/L、1.2×10^-2Bq/L、4.6×10^-2Bq/L;松花江水为6.2×10^-3Bq/L、6.2×10^-3Bq/L、3.0×10^-4Bq/L、1.1×10^-2Bq/L、2.7×10^-2Bq/L。我省成年男子对²³⁸U、²³⁴U、²³²Th和²²⁶Ra的人口加权年摄入量分别我:36Bq、36Bq、5.2Bq、65Bq。由这四种核素所致人口加权年有效待积剂量当量是28μSv。     

147Pm β射线对人类呼吸道上皮毒性作用

采用以前建立的人胎气管支气管段(HFTBs)作异种并位移植用于研究放射性物质毒性或致癌效应的正常人类呼吸道实验模型(NHRT)．取¹⁴⁷Pm金属箔片平面源, 剪成10mm×6mm长方形, 利用⁵⁷Co为刻度源, 经γ能谱测试确定该源β射线放射性活度为5.63×l0⁸Bq。并将期以6mm为周长卷成圆筒，以利于置入已移植的HFTBs腔内.根据源表面金箔及HFTBs管壁受照厚度，估算HFTBs管壁组织受照平均剂量率为2.82Gy/h,结果发现，受到母射线照射后HFTBs粘膜上皮均发生不同程度破 坏:2周时上皮修复;4周可见多处鳞状化生;8周时己见到广泛性的角化鳞状化生.本文并讨论了NHRT与其它实验模型作比较(如吸入，植埋)本身具有的优点。     

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.}     

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.     

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.     

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。     

Molecular structures involved in 67Ga and 59Fe binding by placenta and tumors

The binding of ⁶⁷Ga and ⁵⁹Fe by placenta and tumors was compared. After sonification, about 50% of the total radioactivity was present in the insoluble fraction consisting of heavy subcellular particles (mitochondria, fragments of membranes, nuclei, etc.) and known to be rich in lipo- and glycoproteins. Heat denaturation and gel filtration were used to study transferrin and ferritin distribution in the supernatant. The differences between ⁵⁹Fe and ⁶⁷Ga uptake in this supernatant seemed to indicate that the transferrin-ferritin system plays a less important role in ⁶⁷Ga binding than in ⁵⁹Fe binding.     

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.     

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

Purpose For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with ⁹⁰Y is frequently used [⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide (considered as the gold standard) and the commercially available ¹¹¹In-pentetreotide.Methods The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide, in accordance with the directives of the German radiation protection authorities.Results The range of doses (mGy/MBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide) for kidneys, spleen, liver and tumour masses was 0.6–2.8, 1.5–4.2, 0.3–1.3 and 2.1–29.5 (⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide), respectively, versus 1.3–3.0, 1.8–4.4, 0.2–0.8 and 1.4–19.7 (¹¹¹In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy.Conclusion Compared with ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide, dosimetry with ¹¹¹In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.     

Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET

Purpose Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) and ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients.Methods Binding of ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC and ¹⁸F-FDG PET scans.Results Large numbers of SSTR binding sites for ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas ¹⁸F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/¹⁸F-FDG-negative than were ¹⁸F-FDG-positive/SSTR-negative.Conclusion Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels.These studies were supported in part by the Austrian National Bank (Anniversary Foundation, Projects No. 7487 and 8185) and by a Foundation of the Mayor of the City of Vienna.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer

OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer. METHODS: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1-8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20 vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.