吸入239PuO2对肺损伤效应的研究

本研究选用了806只Wistar大鼠(实验组584只,对照组222只)观察了吸入²³⁹PuO₂(初始肺负荷O.38～12.6kBq,AMADl.1～1.4μm,o_gl.9)后在呼吸道中的沉积与廓清规律,²³⁹PuO₂所致肺癌的量效关系及其组织学特征； 肺巨噬细胚(PAM).肺天然杀伤细胞(NK)及肺泡I型细胞(AT-I)在α粒子作用下功能与形状学改变。结果表明；大鼠终生肺癌的危险度岁,2162/10⁶火鼠·cGy,芏332例8种类型肺癌中以腺癌、鳞癌为主,同时观察到一例胸淋巴结的原发性血管肉瘤。PAM核受到1.0Gy照射后,细胞增殖功能受抑,非特异吞噬功能降低约需大于2.2Gy.在初始肺负荷量4.O～12.9kBq时,NK细胞对YAC-1肿瘤细胞的杀伤活力有下降趋势。通过微剂量学、体视学的研究,证实AT-I细胞可能是α粒子诱发肺癌的靶细胞之一,在初始肺负荷量为250～733Bq时,即可观察到细胞分化程度的下降。文中还对²³⁹PuO₂诱发人肺癌的危险度进行了讨论。     

239PuO2在大鼠呼吸道中的沉积与廓清规律的观察

为了阐明PuO₂在大鼠呼吸道中沉积与廓清规律,提出肺及肺门淋巴结(TLN)剂量计算公式,供有关的剂量一效应研究参考。使160只大鼠吸入²³⁹PuO₂气溶胶(AMAD:1.4μm:og=1.8),然后于378天内分期分批活杀,测定肺、TLN、股骨的²³⁹Pu量。结果表明,PuO₂在大鼠肺泡中：的初始沉积率为24.9±7.2%.肺中PuO₂2的廓清规律呈二项指数函数,其80%和20%分别以122.7和373天的有效半排期廓清。随着肺中钚含量的不断减少,TLN中钚的蓄积量不断增加,两者呈一定的函数关系。从而推导出肺和TLN剂量计算公式。骨中含钚量很少。本文还斌肺中PuO₂向TLN转移的问雹进行了讨论。     

出生前注入氚水和γ射线照射诱发大鼠脑细胞缺失的相对生物效应研究

对两组妊娠11天的大鼠分别注入氚水(HTO)和以¹⁸⁷CsY射线连续照射, 以仔鼠出生后18天时大脑皮质锥体细胞数的变化为生物终点, 观察两种辐射的剂量效应曲线, 并将两者比较, 求出氚的RBE值。结果表明，在两种射线照射下，仔鼠大脑锥体细胞数皆随剂量增加而减少(P＜0.01).仔鼠受β和137Csγ射线照射,吸收剂量范围分别为0.012～1.32Gy,大脑锥体细胞缺失率Y与计量D均可拟合成对数直线回归方程,Y_β=27.1+8.3LgD和Y_p=18.5+13.9LgD.氚吸收剂量为1.7～0.17Gy时RBE值为3.4～8.5.     

大鼠吸入239PuO2在肺巨噬细胞内的代谢

为了解核素对靶细胞的剂量与效应的关系,本实验用成年雄性大鼠,日龄75～80日,体重180～225克,令大鼠吸带有钚浓度为9.2×10^-9～5.5×10⁸Ci/l的气溶胶。实验结果表明:大鼠吸入²³⁹PuO₂后40分钟,由肺可洗出钚的76%在肺巨噬细胞(PM)内,1天后可达96%。洗出细胞中PM吞噬钚的指数随动物初始肺沉积量增加而增加。本实验给出了吸钚后28天以内,肺钚滞留函数式和PM内钚滞留函数式。这些可作为估算肺与PM内剂量的参考。     

吸入239PuO2致癌危险度实验中的剂量计算

钚在肺中的初始沉积量,钚在呼吸道的代谢规律以及靶器官质量是吸入²³⁹PuO₂致癌危险度实验研究中器官剂量计算的三要素。本文作者提出了大鼠暇入²³⁹PuO₂后肺、肺门淋巴结剂量计算公式 。此公式因考虑到靶器官质量变化规律, 优于国外算法,使器官剂量估算更合理。     

131I及132I在大鼠甲状腺的比较效应

甲状腺吸收剂量¹³¹I各组为25,59、92Gy;¹³²I各组为7、14,29Gy。结果表明,各剂量组甲状腺滤泡长,宽乘积与对照组相比,除不给MTU的25Gy组(A₁)外,其他各组均随吸收剂量增加而相应减少(P<0.01,P<0.001)。甲状腺重量/体重与吸收剂量呈幂函数关系。     

131I及132I对大鼠甲状腺致肿瘤效应

233只成年及断乳的纯种Wistar大鼠,一次腹腔注射不同剂量¹³¹I或¹³²I,对照大鼠同对注射灭菌生理盐水。实验结果表明,¹³²I致甲状隙肿瘤效应约为¹³¹I的6倍。如甲状腺肿癌发生率为50%,60%及70%时,¹³¹I中毒鼠所需的甲状腺吸收剂量(29、34及44Gy)约为¹³²I中毒鼠剂量(4.5,6及8Gy)的6倍。同一核素对断乳鼠的致肿瘤效应为成年鼠的1.1倍。如甲状腺吸收剂量相同(13Gy及60Gy)时,断乳鼠肿瘤发生率各为94%等及76%成年鼠为88%及72%两种碘核素致大鼠甲状腺肿痛效应的最适照射剂量;¹³¹I为59Gy、¹³²I为13Gy.     

125I 131I 132I在大鼠甲状腺内的代谢参数及累积吸收剂量

本文报道¹²⁵I、¹³¹I、¹³²I在大鼠甲状腺内的代谢参数并计算了甲状腺对上述3种同性豢的最大吸收率,有效半减期和累积吸收剂量及其它有关的参数。在大鼠腹腔内分别注入¹²⁵I(NaI)溶液8.08μCi,¹³¹I溶液0.99μCi,¹³²I溶液12.2μCi,然后测得甲状腺的吸碘率分别为33%,17%和12%,最后计算得出犬鼠甲状腺的累积吸收剂量分别为7.94,3.09和2.58Gy,每注入1μCi的放射性碘同位索,大鼠甲状腺的平均吸收剂量分别为0.98、3.12和0.2lGy.     

18氟-氟代脱氧葡萄糖对Lewis肺癌细胞增殖的影响

目的 研究不同浓度¹⁸氟-氟代脱氧葡萄糖(¹⁸F-FDG)对Lewis肺癌细胞增殖的影响,探讨其作用机制。方法 以0、0.37、1.85、3.70 和 7.4 (×10⁶ Bq/ml) ¹⁸F-FDG处理细胞24 h,用倒置显微镜与电子显微镜观察细胞形态学改变,流式细胞术检测细胞凋亡与细胞周期时相分布,³H-TdR掺入法检测细胞DNA合成,比色法检测细胞脂质过氧化水平,免疫组织化学法检测细胞Bcl-2和Bax蛋白的表达。结果 细胞的累积吸收剂量分别为0、0.11、0.55、1.10与2.20 Gy。受照细胞出现凋亡形态学改变,在0～2.20 Gy剂量范围内,细胞凋亡率由(4.05±0.01)%增大为(25.6±0.28)%(t=188, P<0.01),³H-TdR掺入率从100%下降为(22.0±0.51)%( t=27.6, P<0.05),细胞内丙二醛(MDA)含量由(0.08±0.03)上升到(0.67±0.12)μmol/L(t=11.7, P<0.01)。Bcl-2蛋白表达降低,Bax蛋白表达增高,细胞周期发生G₂/M期阻滞。结论 ¹⁸F-FDG能诱导Lewis肺癌细胞凋亡,抑制细胞增殖。     

131I大鼠甲状腺致癌作用的病理学研究

本文报道用雄性Wistar大鼠409只,腹腔分别注射¹³¹I 52.4、40.0、26.2; 12.5和2.5μCI／只,两年的观察结果。五个剂量组甲状腺吸收剂量分别为164、125、82、39和7.8Gy.12个月发生甲状腺良性瘤,观察到24个月时,39Gy以上各剂量组主要表现为耳状腺退行性变和良性癌生成;而7.8Gy剂量组甲状腺恶性瘤发生率达45.8%。¹³¹I诱发大鼠甲状腺良性肿瘤以滤泡性腺癌为主,其次是乳头状腺癌,恶性瘤以乳头状腺癌和混合癌为主,甲状腺肿瘤的发生与¹³¹I对甲状腺滤泡上皮细胞损伤、修复;在甲状腺轴内分泌紊乱(T₄降低、TSH升高)情况下,TSH反复刺激损伤的甲状腺上皮细胞有关。     

广东高本底地区部分中学生血清乙型肝炎表面抗原(HBsAg)的检测

本文应用RIA(放射免疫分析)研究了1.5月龄的雄性Wistar大鼠腹腔注射无载体医用Na¹³¹I溶液后甲状腺功能的改变.结果表明,甲状腺吸收剂量较低的7.8Gy和39.0Gy组,血清T,和T₄水平略高于对照组,剂量较高的82.0Gy和164.0Gy组,血清T₃,和T₄.水平明显低于对照值.血清r-TSH水平随甲状隙吸收剂量的增加明显升高,表明大鼠发生了原发性甲状腺功能低卞.根据镜下观察的组织学类型,T₃、T₄和r-TSH水平的统计分析表明,血清T₃,无明显变化,T₃水平的降低和r-TSH水平的升高似与甲状腺组织学改变有-定关系.     

双示踪剂PET-CT在头颈部肿瘤生物适形调强放疗的初步研究

目的 探讨¹⁸F-脱氧葡萄糖（¹⁸F-FDG）和¹⁸F-赤硝基咪唑（¹⁸F-FETNIM）双示踪剂PET-CT确定头颈部肿瘤生物适形调强放射治疗（BIMRT）靶区的可行性。方法 经病理证实且未经治疗的头颈部肿瘤患者12例,治疗前行CT模拟定位扫描、¹⁸F-FDG PET-CT和¹⁸F-FETNIM PET-CT扫描,分别勾画大体肿瘤靶区（GTV_CT）、葡萄糖代谢亚靶区（GTV_FDG）、乏氧亚靶区（GTV_FETNIM）,测量并比较原发肿瘤和转移性淋巴结体积,分别表示为GTV_P-CT、GTV_N-CT、GTV_P-FDG、GTV_N-FDG、GTV_P-FETNIM 和GTV_N-FETNIM。 结果 12例患者原发肿瘤和转移淋巴结均摄取¹⁸F-FDG,SUVmax-P和SUVmax-N分别为12.3±5.5和 5.1±2.8。9例患者原发肿瘤摄取¹⁸F-FETNIM,其中5例患者转移性淋巴结有摄取,未见摄取4例;3例患者原发肿瘤未见¹⁸F-FETNIM 摄取,其中转移性淋巴结有摄取1例,未见摄取2例。GTV_P-CT、GTV_P-FDG 和GTV_P-FETNIM分别为 （22.23±12.11）、（20.83±11.59）和（1.98±1.81）cm³,GTV_N-CT、GTV_N-FDG 和GTV_N-FETNIM分别为 （10.77±8.87）、（10.41±8.61）和（0.61±1.08）cm³。GTV_P-FETNIM < GTV_P-CT,GTV_P-FETNIM < GTV_P-FDG,GTV_N-FETNIM < GTV_N-CT,GTV_N-FETNIM < GTV_N-FDG（P<0.01）,GTV_P-CT与GTV_P-FDG、GTV_N-CT与GTV_N-FDG差异无统计学意义。结论 不同示踪剂PET-CT显像反映肿瘤细胞不同方面的生物学信息,根据PET-CT影像所显示的示踪剂高摄取区域将肿瘤组织划分为若干个子区域是可行的,为实现生物调强放疗提供了可靠的研究基础。     

Determination of k0-values for the reactions Zr (n, γ) Zr and Zr (n, γ) Zr–Nb by irradiation in highly thermalized neutron flux

Determination of k₀-factors for zirconium isotopes was performed by co-irradiation of Zr and Au–Al. Due to the highly thermalized irradiation position at FRM-II, interferences from epithermal neutrons were found largely decreased for ⁹⁶Zr (n, γ) ⁹⁷Zr–^97mNb, the reaction with the highest Q₀-value in all (n, γ) reactions. Results showed that, the ⁹⁵Zr k₀-values from this work were the same as the recommended ones. For ⁹⁷Zr–^97mNb 743.4 keV gamma-line, the new k₀-value was 2.8% higher compared to the recommended value, which is not a significant difference. These results are helpful in clarifying the suspicion about the Zr k₀-factors.     

C hyperfine interactions of CO2 in irradiated tooth enamel as studied by EPR

The EPR spectrum of tooth enamel caused by ¹³C hyperfine interactions of the CO₂⁻ radical were studied on γ-irradiated powdered samples annealed for 40 min at different temperatures up to 250°C. The lineshape and hyperfine splitting of the spectra were found to depend on the annealing temperature. Experimental spectra were compared with calculated ones assuming that EPR spectra are formed by two CO₂⁻ species—axial (rotating) and orthorhombic (braked) radicals. We assumed that the axial CO₂⁻ radicals are centers located in perfect areas of the hydroxyapatite crystals of tooth enamel whereas the orthorhombic CO₂⁻ radicals are rotating centers which are braked by defects. The thermal treatment of enamel samples leads to defective annealing and transformation of the orthorhombic centers into axial ones. This results in an increasing axial CO₂⁻ radical contribution to the EPR spectrum with increase of annealing temperature.     

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。     

Carbon-11 pb-12: an attempt to visualize the dopamine d4 receptor in the primate brain with positron emission tomography

The dopamine D₄ receptor (D₄R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a novel, high-affinity ( K_i=0.040 nM) and selective D₄R ligand. We radiolabeled PB-12 with carbon-11 (t_1/2 20.4 min) by O-methylation of the corresponding desmethyl analogue N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-hydroxybenzamide (LM-190) with [¹¹C]methyl triflate. Derivative LM-190 was prepared by condensing 3-hydroxybenzoic acid with the appropriate amine. For the radiolabeling, the incorporation yield was >90% and the total synthesis time including high performance liquid chromatography (HPLC) purification was about 35 min. The specific radioactivity of [¹¹C]PB-12 at time of injection was 67–118 GBq·μmol⁻¹. PET studies in a cynomolgus monkey showed a high uptake and widespread distribution of radioactivity in the brain, including the neocortex and thalamus. About 40% of total radioactivity in plasma represented unchanged radioligand at 60 min after injection as determined by HPLC. Pretreatment with the D₄R ligand 3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrollo[2,3-b]pyridine (L-745,870) prior to radioligand injection failed to demonstrate receptor-specific binding in the monkey brain. Furthermore, the brain radioactivity distribution was left unaffected by pretreating with unlabeled PB-12. This failure to detect a D₄R-specific signal may be related to a very low density of the D₄R in primate brain, insufficient binding affinity of the radioligand, and a high background of nonspecific binding. It can be concluded from these findings that [¹¹C]PB-12 is not suitable to visualize the D₄R in the primate brain with PET.     

Improved Stability and Practicality for Synthesis of 4-Borono-2-[18F]fluoro-l-phenylalanine by Combination of [18O]O2 Single-Use and [18F]CH3COOF Labeling Agents

Purpose4-Borono-2-[¹⁸F]fluoro-l-phenylalanine ([¹⁸F]FBPA) synthesized with [¹⁸F]F₂, produced using the ¹⁸O(p, n)¹⁸F reaction, has been reported for increasing radioactivity. However, a dedicated system and complex procedure is required to reuse the costly [¹⁸O]O₂ gas; also, the use of [¹⁸F]F₂ as a labeling agent reduces the labeling rate and radiochemical purity. We developed a stable and practical method for [¹⁸F]FBPA synthesis by combining [¹⁸F]F₂, produced using a [¹⁸O]O₂ single-use system, and a [¹⁸F]CH₃COOF labeling agent.MethodsThe produced [¹⁸F]F₂ was optimized, and then [¹⁸F]FBPA was synthesized. For passivation of the target box, 0.5% F₂ was pre-irradiated in argon. Gaseous products were discarded; the target box was filled with [¹⁸O]O₂ gas, and then irradiated (first irradiation). Then, the [¹⁸O]O₂ gas was discarded, 0.05–0.08% F₂ in argon was fed into the target box, and it was again irradiated (second irradiation). The [¹⁸F]F₂ obtained after this was passed through a CH₃COONa column, converting it into the [¹⁸F]CH₃COOF labeling agent, which was then used for [¹⁸F]FBPA synthesis.ResultsThe mean amount of as-obtained [¹⁸F]F₂ was 55.0 ± 3.3 GBq and that of as-obtained [¹⁸F]CH₃COOF was 21.6 ± 1.4 GBq after the bombardment. The radioactivity and the radiochemical yield based on [¹⁸F]F₂ of [¹⁸F]FBPA were 4.72 ± 0.34 GBq and 12.2 ± 0.1%, respectively. The radiochemical purity and molar activity were 99.3 ± 0.1% and 231 ± 22 GBq/mmol, respectively.ConclusionWe developed a method for [¹⁸F]FBPA production, which is more stable and practical compared with the method using [¹⁸O]O₂ gas-recycling and [¹⁸F]F₂ labeling agent.     

[99mTc]Demotate 2 in the detection of sst2-positive tumours: a preclinical comparison with [111In]DOTA-tate

Purpose The aim of this study was to evaluate [^99mTc]Demotate 2 ([^99mTc-N₄ ^0-1,Asp⁰,Tyr³]octreotate) as a candidate for in vivo imaging of sst₂-positive tumours and to compare it with [¹¹¹In]DOTA-tate ([¹¹¹In-DOTA⁰,Tyr³]octreotate). Methods Labelling of Demotate 2 with ^99mTc was performed at room temperature using SnCl₂ as reductant in the presence of citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods. Peptide conjugate affinities for sst₂ were determined by receptor autoradiography on rat brain cortex sections using [DOTA⁰,¹²⁵I-Tyr³]octreotate as the radioligand. The affinity profile of Demotate 2 for human sst₁–sst₅ was studied by receptor autoradiography in cell preparations using the universal somatostatin radioligand [¹²⁵I][Leu⁸,(D)Trp²²,Tyr²⁵]somatostatin-28. The internalisation rates of [^99mTc]Demotate 2 and [¹¹¹In]DOTA-tate were compared in sst₂-positive and -negative control cell lines. Biodistribution of radiopeptides was studied in male Lewis rats bearing CA20948 tumours. Results Peptide conjugates showed selectivity and a high affinity binding for sst₂ (Demotate 2 IC₅₀=3.2 nM and DOTA-tate IC₅₀=5.4 nM). [^99mTc]Demotate 2, like [¹¹¹In]DOTA-tate, internalised rapidly in all sst₂-positive cells tested, but not in sst₂-negative control cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed high and specific uptake in the sst₂-positive organs and in the implanted tumour and rapid excretion from non-target tissues via the kidneys. Conclusion [^99mTc]Demotate 2, similarly to the known sst₂-targeting agent [¹¹¹In]DOTA-tate, showed promising biological qualities for application in the scintigraphy of sst₂-positive tumours.     

56Fe17+、12C6+重离子束照射后人淋巴细胞基因转录谱的改变

目的 探讨重离子束照射对人淋巴细胞基因转录谱的改变。方法 人淋巴细胞Peng-EBV分别经0.1、0.5和2 Gy ⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束照射后,提取各实验组细胞总RNA,利用Agilent人表达谱基因芯片进行基因转录谱的检测并筛选差异表达基因;对差异表达基因进行GO分析;利用KEGG数据库对差异表达基因进行通路分析。结果 Peng-EBV细胞系经⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束照射后,0.1、0.5和2.0 Gy剂量组共同差异表达基因分别为101、199和229个。3个剂量组共同差异表达基因14个,其中,GPSM1、TSPYL5、WFDC2、LAD1等基因在两种离子束各剂量组呈现特征性差异表达。0.1和0.5 Gy剂量组涉及主要基因功能包括细胞粘连、胞外基质构建等,参与的显著性Pathway通路分别为3和6条,主要为细胞因子受体相互作用通路等。2 Gy剂量组主要基因功能包括细胞黏连、Rho蛋白信号转导调节等,参与的显著性Pathway通路3条,主要为p53信号通路等。结论 ⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束可诱导人淋巴细胞基因转录谱的改变,且不同剂量重离子可诱发不同的差异表达基因及通路。     

阴离子交换树脂除210Bi技术在90Sr分析中的应用

目的 为了克服现有分析标准推荐的硫化铋沉淀法除铋存在的弊端,提升分析结果质量。方法 基于201×7阴离子交换树脂设计了除铋实验流程,并通过加标样品和国际原子能机构（IAEA）国际比对样品分析予以验证。结果 采用阴离子交换树脂进行除铋。在锶、钇、铋去除实验中,锶和钇的化学回收率可分别达到（98.6±0.8）%和（98.5±0.7）%,且未发现有Bi₂S₃沉淀生成;在加标土壤分析中,所得到的分析结果与理论值的相对标准偏差为-2.97%~5.94%,优于标准除铋方法的3.96%~17.80%;采用IAEA国际比对样品进行验证,⁹⁰Sr的报出值与目标值的相对标准偏差介于3.40%~7.09%,结果均可接受。结论 阴离子交换树脂对铋能够实现很好的定量去除,同时不吸附锶和钇。另外,阴离子交换树脂的除铋溶液体系与⁹⁰Sr分析时的解吸体系相同,无需转换体系即可实现快速除铋的目的。与现行标准分析方法相比,基于阴离子交换树脂定量除铋是可行的且更优,能够满足⁹⁰Sr常规分析工作需求。