正电子显像剂18F-FDG TracerlabFX-FDG法的制备与质量控制

目的 探讨TracerlabFX-FDG法18F-脱氧葡萄糖(18F-FDG)的制备和质量控制方法.分析影响18F-FDG合成效率的因素.方法 应用美国GE公司的加速器PETtrace,通过18O(p,n)18F核反应生产18F负离子,通过亲核取代反应合成18F-FDG,并对制备的18F-FDG注射液进行质量控制.结果 采用TracerlabFX-FDG法制备18F-FDG,产率较高,可达65%～70%,高效液相色谱(HPLC)法测定的放射化学纯度、化学纯度均大于99%.结论 18F-FDG注射液完全满足临床正电子发射断层显像(PET/CT)的检查需要.     

Explora FDCA制备^18F-FDG、质量控制及影响因素探讨

目的研究正电子药物^18F-FDG的制备与质量控制以及影响^18F-FDG合成效率的因素。方法使用医用回旋加速器,通过^18O（p,n）18F核反应,采用Explora FDG4全自动合成系统制备了^18F-FDG静脉注射液,对于制备的药物进行质量控制与影响因素分析。结果Explora FDG4合成效率65％,^18F-FDG放化纯度99％^18F-FDG其他指标符合药典质量要求,反应体系中残留的水等影响合成效率。结论制备的^18F-FDG静脉注射液使用临床PET-CT检查。     

Explora FDG4制备18F-FDG、质量控制及影响因素探讨

目的 研究正电子药物18F-FDG的制备与质量控制以及影响18F-FDG合成效率的因素.方法 使用医用回旋加速器,通过18O(p ,n) 18 F 核反应,采用Explora FDG4全自动合成系统制备了18F-FDG静脉注射液,对于制备的药物进行质量控制与影响因素分析.结果 Explora FDG4合成效率65%,18F-FDG放化纯度99% 18F-FDG其他指标符合药典质量要求,反应体系中残留的水等影响合成效率.结论 制备的18F-FDG静脉注射液使用临床PET-CT检查.     

采用气相色谱法建立氟[~(18)F]脱氧葡糖注射液中有机溶剂残留的测定方法及其方法不确定度的评价

目的参考中国药典对氟[~(18)F]脱氧葡糖注射液的质量控制要求,建立对氟[~(18)F]脱氧葡糖注射液中有机溶剂残留的测定方法及其方法不确定度进行评定。方法以SUPELCOSPB-5型毛细管柱作为分离柱,采用气相色谱法对PET示踪剂2-~(18)F-2-脱氧-葡萄糖(~(18)F-FDG)合成制备工艺中所使用的有机溶剂乙腈和乙醇进行定量检测。并对~(18)F-FDG中有机溶剂残留的测定方法的不确定度进行初步评价。结果该药品中两种有机溶剂乙腈及乙醇的残留量在分离柱的保留时间10min;采用此方法随机检测了5批次~(18)F-FDG产品,检测结果显示,~(18)F-FDG中含乙醇0.078g/L,乙腈0.079g/L,均符合2015版《中国药典》中对残留溶剂的限度要求。结论应用气相色谱法对~(18)F-FDG中乙腈和乙醇残留物的快速、定量测定具有良好的重复性,并且分析准确、迅速;对~(18)F-FDG中有机溶剂残留的测定方法的不确定度进行了初步分评价。     

18F-氟乙基胆碱的自动化合成、质量控制及初步应用

目的 研究正电子放射性药物2-18F-氟乙基胆碱(18F-FECH)的制备、质量控制以及初步应用.方法 使用MINItrace回旋加速器,通过18O(p,n)18F核反应,采用Tracelab FXFN全自动合成装置制备18F-FECH注射液,对制备的药物进行质量控制,并进行了前列腺癌方面的初步应用.结果 18F-FECH 合成总时间约50 min,放化产率约为30%,放化纯度大于95%,其他指标均符合药典质量要求,显像效果极佳,对前列腺癌与前列腺增生的鉴别诊断有重要意义.结论 制备的18F-FECH注射液可用于临床PET-CT检查,有望成为诊断前列腺癌的新型PET显像剂.     

~(18)F-氟脱氧葡萄糖注射液硅胶TLC分析

目的:建立18F-氟脱氧葡萄糖(18F-FDG)注射液的硅胶薄层色谱(TLC)分析方法。方法:采用TLC分析方法,其中供试品溶液分别为18F-FDG注射液(A)和18F-FDG注射液-无水乙腈(5∶95,V/V)混和溶液(B),固定相为GF型和G型硅胶TLC板,流动相为乙腈-水(95∶5,V/V)。结果:当供试品溶液为A时主峰Rf值波动较大;为B时主峰Rf为0.38~0.40,放化含量均大于98%,放射性杂质18F-离子和副产物18F-氟脱氧甘露糖的Rf分别为0.0和0.78。结论:当供试品溶液为B时,硅胶TLC分析方法稳定、重现性好,其结果与《美国药典》基本相符,且与所用硅胶板种类无关。     

固相萃取合成PET-CT肿瘤探针2-[18F]-2-脱氧-β-D-葡萄糖及其影响因素初探

目的 探讨常见肿瘤显像剂2-[18F]-2-脱氧-β-D-葡萄糖([18F]-FDG)在西门子Explora One化学合成模块上全自动合成方法、质量控制以及影响因素.方法 西门子Eclipse RD回旋加速器生产出[18F-]与以三氟甘露糖为前体进行亲核取代反应合成乙酰化[18F]-FDG,高纯氮气推动,Sep-Pak@C18萃取柱吸附中间体,氢氧化钠水解C-18柱上中间产物,经纯化,灭菌最终得到[18F]-FDG注射液.通过薄层色谱法对合成的产品进行放射化学纯度(RCP)检测,肿瘤患者行[18F]-FDG PET-CT扫描.结果 最终合成产物[18F]-FDG的RCP＞ 95％,20 mg的三氟甘露糖可获得未校正合成效率约为60％.结论 使用ABX[18F]-FDG套件,Explora One化学合成模块实现固相萃取法合成PET显像剂[18F]-FDG,合成时间短,稳定快捷.     

18F-脱氧葡萄糖注射液中细菌内毒素的含量测定

目的：建立检测18F 脱氧葡萄糖(18F FDG)注射液中细菌内毒素含量的方法，以控制药品质量。方法：采用动态浊度法，4批18F FDG注射液样品经10倍稀释后进行细菌内毒素的定量测定，计算回收率。结果：18F FDG注射液经10倍稀释后可完全消除对鲎试剂与细菌内毒素的凝集反应的干扰，内毒素含量均＜0.027 EU·mL 1，平均回收率95.0%。结论：该方法简单，准确，可用于定量检测18F FDG注射液中细菌内毒素含量及药品质量的控制。     

^18F-FDG放射化纯度的快速测定

用HPLC和TLC两种方法测量了CTI双管法生产的^18F FDG的放射化学纯度。用TLC方法测未水解的酯含量，HPLC测游离的氟离子。采用糖柱作为分离柱，新的流动相：85%的乙睛，流速为2.5ml/min，^18F离子的保留时间为2.6min，^18F FCG为3.5min,^18F-FDG中游离^18F测量可在5min内完成。     

利用Siemens Explora FDG4化学合成模块合成18F-FDG的方法及质量控制

目的:建立18F-FDG注射剂的合成工艺及质量控制方法.方法:采用西门子公司的Explora FDG4化学合成模块合成可供注射用的18F-FDG.结果:制得18F-FDG注射剂,TLC测定放射化学纯度大于98%,合成效率达58%以上.结论:采用本方法合成18F-FDG注射剂可在满足日常检查需要的同时最大限度的减少工作人员受到的辐射.     

自动化合成N-琥珀酰亚胺-4-[18F]氟苯甲酸酯

目的 合成18F同位素标记蛋白质、配体、多肽类的中间体N-琥珀酰亚胺-4-[18F]氟苯甲酸酯(18F-FB).方法 以乙基-4-三甲胺苯甲酸酯-三氟磺酸盐为反应前体,利用正电子发射断层成像(PET)显像药物2-氟-18-氟-2-脱氧-D-葡萄糖(18F-FDG)合成专用模块TRACERlab FX-FDG和多用合成模块TRACERlab FX-FN及其固相萃取系统,基于控制软件的改造,通过亲核取代、氢氧化钠水解、酯化反应"三步法"合成.结果 合成18F-FB的总放射性合成时间小于80 min,校正后放射化学产率(38±3)%(n=10),放射化学纯度＞99%,与标准品19F-FB行HPLC比对分析,在柱平均保留时间Tr=8.515 min,两者保留时间基本吻合.结论 此法可以成功合成18F-FB,合成工艺成熟稳定,完全实现了自动化合成,为成功实现18F同位素标记蛋白、多肽类大分子物质进而实现PET成像提供了良好条件.     

阿尔茨海默病正电子显像剂11C-PIB的自动化合成

目的：建立简便的全自动化生产正电子放射性示踪药物2-（4＇-N-11C-甲胺基苯）-6-羟基苯并噻唑（11C-PIB）的方法,满足临床诊断需要。方法：采用气相法制备11C-CH3I,11C-CH3I通过灼热的三氟磺酸银粉末转换成11C-Triflate-CH3,然后与前体2-（4＇-氨基苯基）-6-羟基苯并噻唑在室温发生反应,反应混合液经半制备HPLC分离后再通过Sep-Pak C18分离柱进行固相萃取,并用0.9%无菌氯化钠溶液稀释,最后通过0.22μm的微孔无菌滤膜过滤得到注射液。结果：合成时间从加速器轰击结束开始共35 min,放化产率经过衰减校正后为48.6%（n=25）,化学纯度大于97%,放化纯度大于99%。产品的无菌及无热原要求均符合规定。结论：通过计算机远程控制实现了11C-PIB注射液的全自动生产,简化了生产步骤,保证了生产的可行性和重现性,可完全满足临床需要。     

心脏神经受体显像剂11C标记羟基麻黄素合成方法优化

目的：建立简便实用的正电子放射性示踪药物11C标记的羟基麻黄素（11C-mHED）自动化生产的方法,满足临床诊断需要.方法：首先使用加速器通过14N（p,α）11C核反应来生产11C-CO2,然后使用TRACERlab FXc合成模块将11C-CO2还原为11C-CH4,进一步反应生成11C-CH3I,以此作为甲基化试剂,与间羟胺前体反应得到11C-mHED的混合液,经HPLC进行纯化并用0.9%氯化钠溶液稀释,通过0.22 μm的微孔无菌滤膜过滤得到所需的注射液.结果：合成时间从加速器轰击结束开始共33 min,放化产率经过衰减校正后为12%±1%（n=5）,化学纯度大于97%,放射化学纯度大于99%.产品的无菌及无热原要求均符合规定.结论：通过对比不同文献的方法和修改多个反应参数,简化了生产流程,节省了合成时间,实现了11C-mHED注射液的计算机远程控制全自动生产,保证了生产的可行性和重现性,可完全满足临床需要.     

Facile and improved synthesis of [11C]Me‐QNB

[¹¹C]Me‐QNB is a muscarinic acetylcholinergic receptor antagonist that has been used for the assessment of myocardial muscarinic receptors density in different cardiovascular pathologies. In the current technical note, we report a facile, highly efficient and fully automated method for the preparation of this radiotracer. The radiosynthesis was performed by reaction of [¹¹C]CH₃I with the desmethylated precursor (QNB) at room temperature using the captive solvent method. Excellent radiochemical yield (91.1 ± 2.4%, decay‐corrected) and radiochemical purity (>99.5%), and good specific activity (137 ± 5 GBq/µmol) were obtained when the purification was performed by reverse phase HPLC in overall synthesis time <31 min. Purification using solid‐phase extraction offered lower radiochemical yield (27.6 ± 3.1%, decay‐corrected) and radiochemical purity (>95%) but higher specific activity (244 ± 18 GBq/µmol) in shorter reaction times (<21 min). These results, especially concerning radiochemical yield, significantly improve those previously reported in which the reaction was performed in a vial and the purification step was based on ionic chromatography.     

A novel versatile precursor suitable for 18F‐radiolabeling via “click chemistry”

As an effort to improve ¹⁸F‐radiolabeling of biomolecules in method robustness and versatility, we report the synthesis and radiolabeling of a new azido precursor potentially useful for the so‐called “click reaction,” in particular the ligand‐free version of the copper(I)‐catalyzed alkyne‐azide cycloaddition. The new azido precursor may help to overcome problems sometimes exhibited by most of the currently used analogues, as it is safe to handle and it displays long‐term chemical stability, thus facilitating the development of new radiolabeling procedures. Moreover, the formed ¹⁸F‐labeled 1,2,3‐triazole is potentially metabolically stable and could enhance the in vivo circulation time. The above azido precursor was successfully radiolabeled with ¹⁸F, with 51% radiochemical yield (nondecay‐corrected). As a proof of concept, the ¹⁸F‐labeled azide was then tested with a suitable alkyne functionalized aminoacid (l ‐propargylglycine), showing 94% of conversion, and a final radiochemical yield of 27% (>99% radiochemical purity), nondecay‐corrected, with a total preparation time of 104 minutes.     

Radiosynthesis of novel N-18F-labeled 18F-FHex-α-l-Glu and 18F-FHex-β-Glu

N-¹⁸F-labeled amino acids are important substitutes for new positron emission tomography (PET) imaging tracers complementing the deficiency of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). In this work, two novel N-6-¹⁸F-alkyl amino acid imaging agents, ¹⁸F-FHex-α-l -Glu and ¹⁸F-FHex-β-Glu, were designed and synthesized as potential probes for PET imaging of tumors. ¹⁸F-FHex-α-l -Glu was synthesized using the precursor 6 from ¹⁸F-F⁻ with the yield of 16 ± 4% (n = 5, uncorrected) within about 50 minutes. The specific activity was 14.5 GBq/μmol, and the radiochemical purity was more than 95%. ¹⁸F-FHex-β-Glu was synthesized using the precursor 12 based on ¹⁸F-F⁻ with the yield of 11 ± 3% (n = 3, uncorrected) in about 60 minutes. The specific activity was 9.1 GBq/μmol, and the radiochemical purity was more than 95%.     

Efficient Radiosynthesis of 2-[18F]Fluoroadenosine: A New Route to 2-[18F]Fluoropurine Nucleosides

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Rapid synthesis of [18F]fluoroestradiol: remarkable advantage of microwaving over conventional heating

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