优化18F-FHBG自动化合成方法及其质量评估

目的 优化¹⁸F-FHBG的合成方法,并评估合成¹⁸F-FHBG的质量稳定性。方法 自行设计¹⁸F-FHBG自动化合成流程,待前体N₂-（对甲氧苯基二苯基甲基）-9-[（4-甲苯磺酰基）-3-对甲氧苯基二苯基甲氧基-甲基丁基]鸟嘌呤与¹⁸F^-发生亲核取代反应后,经洗脱、纯化获得¹⁸F-FHBG。记录合成时间,评估合成效率,测定产品放射化学纯度及其体外稳定性,观察其生物分布及PET/CT显像特征。结果 ¹⁸F-FHBG的合成时间为19~25 min,未校正合成效率为（19.00±5.00）%（n>10）;室温放置5、30、60、90、120 min及6 h后,放射化学纯度均>97%。生物分布实验结果显示,¹⁸F-FHBG主要分布于正常昆明小鼠的肝脏、胃肠道及肾脏,脑组织内摄取较少。PET/CT显像结果显示,对新西兰大白兔注射¹⁸F-FHBG后,放射性分布遍及全身较快,注射60 min时显像效果较好。结论 优化的全自动合成方法能快速、高效合成纯度高、稳定性好的¹⁸F-FHBG,适用于PET/CT全身显像。     

Fine‐tuning of the automated [18F]PSMA‐1007 radiosynthesis

Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [¹⁸F]PSMA‐1007 was introduced as an alternative to [⁶⁸Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [¹⁸F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [¹⁸F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield.     

燃煤型氟暴露相关因素在男性不育中的危险度探讨

[目的]探讨燃煤型氟暴露对男性不育的影响。[方法]对227名病例和对照进行与氟暴露相关的生活居住环境、饮食情况、生育情况等的调查,采用Epidata3．O软件建立数据库,然后进行非条件LogiSticlg／归分析筛选危险因素。[结果]燃煤型氟病区男性不育的危险因素包括年龄（OR=3．52）、吸烟（OR=I．75）、主食炉火烘干（0R=4．25）及食用前少淘洗（OR=2．19）;生育能力低下的危险因素包括年龄（OR=5．64）、主食炉火烘干（OR=4．24）及食用前少淘洗（OR=3．77）、喜欢喝自产烘干茶（OR=3．62）;而文化程度（OR=0．37）及主食密闭储存（OR=0．58）则为其保护因素。[结论]煤烟型氟暴露可致男性人群不育的风险升高,主食少用炉火烘干及食用前多淘洗对降低燃煤型氟中毒地区的男性不育风险具有积极的作用。     

氟涂层镁铝合金的体外生物相容性研究简

目的 研究氟涂层镁铝合金的体外生物相容性。方法实验分为空白对照组（N组）、镁铝合金组（M组）、氟涂层镁铝合金组（F组）和阳性对照组（P组）4组。细胞毒性实验：将L929细胞在各组的DMEM浸提液中培养,光学显微镜下观察细胞生长状况。应用WST-1法测量光密度（OD）值。溶血实验：按GB-T16175-2008《医用有机硅材料生物学评价实验方法》第13部分《溶血试验》进行实验。测量各样本的OD值,计算溶血率。豚鼠最大剂量致敏实验,按照GBJ16886.10-2005（（医疗器械生物学评价》第10部分《刺激与迟发型超敏反应试验》进行实验。观察激发阶段去除贴附片后24、48、72h豚鼠皮肤致敏情况。结果各观察期F组的形态分级为0级,M组为4级。各组各观察期内OD值差异均有统计学意义（F=312.96,P=0.000）。第3天,实验组OD值均高于P组（1.050±0.065 vs 0.292±0.010）（P〈0.05）。第5天、第7天,F组与N组OD值（1.429±0.096 vs 1.622±0.156,0.928±0.040 vs 50.995±0.070）处于同一水平（P〉0.05）,均高于P组（0.270±0.015,0.281±0.006）（P〈0.05）。M组溶血率为68.3％,F组为0.8％。24h、48h和72h后N组、M组、F组皮肤均无红斑。结论氟涂层镁铝合金体外实验显示具有良好的生物相容性。     

Boron–18F containing positron emission tomography radiotracers: advances and opportunities

Standard [¹⁸F]fluorination methods to form carbon–fluorine bonds can have some limitations such as low yield and the requirement for harsh reaction conditions. Inorganic approaches include the formation of boron–[¹⁸F]fluorine bonds and have the potential to give high specific activities at room temperature forming a bond that is stable in vivo. There is considerable potential in future applications, particularly in relation to multimodal imaging and the provision of rapid efficient labelling protocols. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and evaluation of two fluorine‐18 labelled phenylbenzothiazoles as potential in vivo tracers for amyloid plaque imaging

Uncharged derivatives of thioflavin‐T have known in vitro and in vivo affinity for amyloid β. We synthesized and evaluated two derivatives with a fluorine‐18 labelled fluoropropoxy substituent either at the 6‐position or at the 2′‐position of the 2‐(4′‐aminophenyl)‐1,3‐benzothiazole core with the aim to get suitable radiotracers to perform amyloid plaque imaging. The fluorine‐18 labelled compounds were obtained by nucleophilic substitution of the corresponding tosyl precursors with [¹⁸F]fluoride with a radiochemical yield of 50%, yielding 6‐(3′′‐[¹⁸F]fluoropropoxy)‐2‐(4′‐aminophenyl)‐1,3‐benzothiazole ([¹⁸F]2) and 2‐[2′‐(3′′‐[¹⁸F]fluoropropoxy)‐4′‐aminophenyl]‐1,3‐benzothiazole ([¹⁸F]3) with a specific activity between 33 and 51 GBq/µmol. The identity of the radiolabelled compounds was confirmed using radio‐LC‐MS and by comparing retention times on RP‐HPLC. Biodistribution studies in healthy mice showed for both compounds a relatively high initial brain uptake, which was significantly higher for [¹⁸F]2 than for [¹⁸F]3 (4.5% ID/g versus 3.0% ID/g, p<0.05). Wash‐out from control brain was faster for [¹⁸F]3. In vitro binding affinity tests using human AD brain homogenates revealed that only compound 2 has affinity for fibrillar amyloid β (K_i=14.5 nM). This was confirmed by the incubation of transgenic APP mouse brain sections with the cold compounds, where 3 did not stain any structure whereas 2 stained amyloid plaques present in APP mouse brain. These data suggest that [¹⁸F]2 may be a useful tracer for in vivo visualization of fibrillar amyloid β. Copyright © 2009 John Wiley & Sons, Ltd.     

钙基型煤固氟效果实验研究

目的在燃煤型地方性氟中毒病区,研究钙基固氟剂对燃煤中的氟固氟效果。方法在高氟煤中加入适宜比例钙基固氟剂制成型煤,将高氟煤中的氟固定在煤渣中,减少其在空气中的释放;同时测定型煤中各组分和煤渣中的氟含量以及室内空气中氟化物、二氧化硫和PM10的浓度,评价钙基固氟剂的固氟效果及室内空气污染物水平。结果在贵州省贵定县燃煤型氟中毒地区进行30户中试燃煤固氟效果研究,钙基固氟剂平均固氟效率为71.8%;实验组室内空气中氟化合物平均浓度为0.0052mg/m3,与对照组比下降27.8%,低于环境空气质量标准(0.007mg/m3);SO2平均浓度为0.67mg/m3,与对照组比下降52.8%,稍高于室内空气质量标准(0.5mg/m3)。结论使用钙基固氟剂制成的型煤可以减少燃用高氟煤导致的氟污染,改善室内空气污染状况。     

In vivo observation of intracellular oximetry in perfluorocarbon‐labeled glioma cells and chemotherapeutic response in the CNS using fluorine‐19 MRI

Preclinical development of therapeutic agents against cancer could greatly benefit from noninvasive markers of tumor killing. Potentially, the intracellular partial pressure of oxygen (pO₂) can be used as an early marker of antitumor efficacy. Here, the feasibility of measuring intracellular pO₂ of central nervous system glioma cells in vivo using ¹⁹F magnetic resonance techniques is examined. Rat 9L glioma cells were labeled with perfluoro‐15‐crown‐5‐ether ex vivo and then implanted into the rat striatum. ¹⁹F MRI was used to visualize tumor location in vivo. The mean ¹⁹F T₁ of the implanted cells was measured using localized, single‐voxel spectroscopy. The intracellular pO₂ in tumor cells was determined from an in vitro calibration curve. The basal pO₂ of 9L cells (day 3) was determined to be 45.3 ± 5 mmHg (n = 6). Rats were then treated with a 1× LD10 dose of bischloroethylnitrosourea intravenously and changes in intracellular pO₂ were monitored. The pO₂ increased significantly (P = 0.042, paired T‐test) to 141.8 ± 3 mmHg within 18 h after bischloroethylnitrosourea treatment (day 4) and remained elevated (165 ± 24 mmHg) for at least 72 h (day 6). Intracellular localization of the perfluoro‐15‐crown‐5‐ether emulsion in 9L cells before and after bischloroethylnitrosourea treatment was confirmed by histological examination and fluorescence microscopy. Overall, noninvasive ¹⁹F magnetic resonance techniques may provide a valuable preclinical tool for monitoring therapeutic response against central nervous system or other deep‐seated tumors. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Quantitative tissue oxygen measurement in multiple organs using 19F MRI in a rat model

Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar ¹⁹F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO₂) <30 mmHg. It uses the linear relationship between spin‐lattice relaxation rate (R₁) of hexafluorobenzene (HFB) and pO₂. The feasibility of this technique for a wider range of pO₂values and individual organ tissue pO₂ measurement was investigated in a rat model. Spin‐lattice relaxation times (T₁= 1/R₁) of hexafluorobenzene were measured using ¹⁹F saturation recovery echo planar imaging. Initial in vitro studies validated the linear relationship between R₁ and pO₂ from 0 to 760 mmHg oxygen partial pressure at 25, 37, and 41°C at 7 Tesla for hexafluorobenzene. In vivo experiments measured rat tissue oxygen (ptO2) levels of brain, kidney, liver, gut, muscle, and skin during inhalation of both 30 and 100% oxygen. All organ ptO₂ values significantly increased with hyperoxia (P < 0.001). This study demonstrates that ¹⁹F MRI of hexafluorobenzene offers a feasible tool to measure regional ptO2 in vivo, and that hyperoxia significantly increases ptO2 of multiple organs in a rat model. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.