小批量放射性药液自动分装系统解决新型放射性药物研究过程中的小试及中试阶段放射性药液精准定量的自动分装操作.该装置采用旋转型自动化结构设计,体积小巧,工位紧凑,自动化程度较高,符合小型放射性药物箱室的放射性操作的要求.经安装及测试验证,分装精度及分装速度符合放射性药液分装性能.小批量放射性药液自动分装系统可应用于多种核素新药研究的分装工艺过程.

BackgroundCopper[64Cu] chloride solution is commonly used as raw material for the preparation of radiopharmaceuticals, which can be used in PET imaging or as a paired nuclide for tumor theranostic. Quality control test of copper[64Cu] chloride solution for radiolabelling must be done before use, and the radiochemical purity test is the key item of quality control.PurposeThis study aims to establish a rapid and reliable method for radiochemical purity analysis of copper[64Cu] chloride solution, by screening the test conditions of stationary phase and mobile phase.MethodsiTLC-SG silica gel paper plate was used as the stationary phase, and the mixed solution of dichloromethane, acetonitrile, methanol and 0.05 mol∙L-1 HCl was used as the mobile phase. The reference solution was prepared by mixing the test solution with DTPA solution in equal volume. The test solution and the reference solution were loaded on the paper plate separately and developed using the mobile phase. The kinds of stationary phase, composition and proportion of the mobile phase were optimized.ResultsUnder the optimized conditions, the Rf of the test solution is greater than 0.9 and the Rf of the reference solution is less than 0.1, and the separation degree is greater than 1.0, which satisfies the system suitability of thin-layer chromatography (TLC).ConclusionsEstablished method in this study is simple, reliable and rapid for the detection of radiochemical purity of copper[64Cu] chloride solution, and complying with the technical requirements of European pharmacopoeia for the determination of radionuclide solution for radiolabelling.

The radiolabeling of somatostatin octapeptide analogue NOTA-NOC with 64Cu was carried out. The preliminary study of 64Cu-NOTA-NOC on the in vitro stability, the lipid-water partition coefficient, and the distribution in normal and tumor-bearing mice was conducted. The labeling and quality control methods of 64Cu-NOTA-NOC were developed. The in vitro stability of 64Cu-NOTA-NOC was investigated in buffer solution and 10% fetal bovine serum solution at 37 ℃. The lipid-water partition coefficient of 64Cu-NOTA-NOC was also determined. Biodistribution studies were performed in normal KM mice and nude mice bearing BON-1 tumor and small-animal PET imaging studies were performed on nude mice bearing BON-1 tumor. The results showed that radiolabeling of NOTA-NOC with 64Cu was straightforward and fast (～15 min) at room temperature in high yield and >95% of radiochemical purity. 64Cu-NOTA-NOC showed good stability in buffer solution and 10% fetal bovine serum solution at 37 ℃. The value of LogP was -1.12±0.005 6 which indicated 64Cu-NOTA-NOC was hydrophilic. Biodistribution studies in normal mice revealed high uptake of radioactivity in kidneys, suggesting that 64Cu-NOTA-NOC was mainly metabolized by the kidneys, and the blood uptake decreases significantly 4 h, indicating rapid blood clearance rate. 64Cu-NOTA-NOC was mainly metabolized by the kidney in nude mice bearing BON-1 tumor. At 1 h, 2 h, 4 h, tumor uptake was (3.74±1.23)%ID/g, (4.80±0.92)%ID/g and (1.31±0.27)%ID/g respectively, and tumor/muscle ratio reached to 10.38 at 2 h. The results of PET/CT imaging of nude mice bearing BON-1 tumor showed that the tumor uptake of 64Cu-NOTA-NOC peaked at 1 h, which was 7.7%ID/g，and after co-administration of the blocker, the tumor uptake of 64Cu-NOTA-NOC was significantly reduced to 0.94%ID/g. 64Cu-NOTA-NOC could be prepared under mild reaction conditions; and it had good stability in buffer solution and 10% fetal bovine serum. 64Cu-NOTA-NOC was mainly metabolized by kidneys, and cleared fast from the body in normal mice as well as in model mice. The tumor/muscle ratio could reach 10.38 at 2 h. The results of PET/CT imaging showed that the tumor uptake of 64Cu-NOTA-NOC was specific. These results demonstrated the potential of 64Cu-NOTA-NOC in the diagnosis of SSTR positive tumors, and it is worthy of further evaluation.

为建立放射性-高效液相色谱分析方法测定治疗用碘[131 I]化钠胶囊放射化学纯度,采用十八烷基硅烷键合硅胶填充的色谱柱(4.6 mm×250 mm×5μm),以5.85 g/L氯化钠溶液(加入0.65 mL正辛胺并用稀磷酸调pH至7.0)-乙腈(V:V=20:1)为流动相,串联紫外-可见分光检测器(检测波长为220 nm)与放射性流量检测器,柱温为25℃,运行40 min,1.5 mL/min进行等度淋洗,可有效地将主峰碘[131 I]化物与放射性化学杂质碘[131 I]酸根进行分离,碘[131 I]化物和碘[131 I]酸根分别在0.19～92.50 GBq/L和0.15～4.81 GBq/L活度浓度范围内线性关系良好,相关系数r分别为0.993和0.997,碘[131 I]化物和碘[131 I]酸根的检测限分别为3.21×10-2 GBq/L和4.74×10-2 GBq/L,定量限分别为9.63×10-2 GBq/L和7.91×10-2 GBq/L,回收率为70.0％ ～125.0％,耐用性和精密度良好.该法适用于治疗用碘[131 I]化钠胶囊的放射化学纯度测定,为制定该类药物的质量控制标准提供了技术参考.

64Cu是目前应用十分广泛的放射性核素,主要用于PET诊断.本文基于C30加速器对64Cu核素的制备工艺进行研究.制靶靶片为金属铜材质,在靶片表面镀金膜,以保护铜基底.镀金完成后用HCl和H2O2浸泡镀金层以去除金属杂质,用脉冲电镀法电镀富集64 Ni层.将靶片转移至C30加速器固体靶站进行辐照,束流能量为15.5 MeV.将辐照后的靶片转移至分离纯化热室.在溶靶槽中加入6 mol/L HCl和30％H2O2溶靶,使用AG1-X8阴离子交换树脂分离纯化,最终获得64Cu核素.分别测定64Cu的放射性核纯度、放射化学纯度、金属杂质含量等质量指标.待收集的64 Ni溶液衰变完全后,使用AG1-X8树脂回收.检验结果显示,富集64Ni厚度约8.5～16.3 mg/cm2,64Cu产能大于37 GBq,产额可达180～250 MBq/(μA·h),放射性核纯度大于99.9％,放射化学纯度大于97.0％,金属杂质含量均小于0.5μg/GBq.64Cu制备工艺稳定、质量可控,达到了规模化生产水平,为64Cu相关药物的研究与开发提供了稳定可靠的核素来源.

Positron computed emission tomography (PET) is an important diagnosis and imaging tool for nuclear medicine with the advantages of high sensitivity, resolution, and safety. It is widely used in the diagnosis of tumors, cardiovascular and cerebrovascular diseases, and so on. 64Cu nuclide has become the focus of research in the field of PET molecular probe and theranostic radiopharmaceuticals due to its suitable half-life (12.7 h), unique decay properties （β+, 0.653 MeV, 17.4%; β-, 0.579 MeV, 39%; electron capture） and the ability to form stable complexes with multiple ligands. Currently, more than 30 clinical studies of 64Cu-radiopharmaceuticals are on going with focus on neuroendocrine tumors, prostate cancer and hypoxic tumors. The results of these clinical trials of 64Cu-radiopharmaceuticals showed that 64Cu-radiopharmaceuticals had high resolution, detection rate and good safety. In addition, the long half-life of 64Cu nuclide allows 64Cu nuclide and 64Cu-radiopharmaceuticals to be transported to distant medical units, which is convenient for dose preparation and clinical practice. This paper selectively reviewed the progresses in clinical research conducted on 64Cu-radiopharmaceuticals in the past decade, hoping to provide some references and ideas for the future research and development of 64Cu-radiopharmaceuticals. It is expected that 64Cu-radiopharmaceuticals will be approved for the diagnosis of neuroendocrine tumors, prostate cancer and other diseases in the near future.

In order to obtain the appropriate target backing material for 64Cu production which will meet radiolabeling requirements, and to reduce the content of stable copper impurity generated from copper target substrate in the final 64Cu product, tantalum is selected as the target backing material. By carrying out a series of experiments including thermal fluid solid coupling analysis, nickel plating experiment, dissolution experiment, irradiation experiment, falling test, thermal shock test on the tantalum target substrate, tantalum target substrate is finally utilized for 64Cu production. The results showed that tantalum target substrate could be applied to 64Cu production, which has simplified the whole production process of 64Cu, the yield can reach 38.1 GBq (EOB) or 190.5 MBq·μA-1·h-1 (EOB). The tests of ［64Cu］CuCl2 solution showed that the radionuclide purity was greater than 99.9%, radiochemical purity was greater than 95% and the metal impurity content was less than 1.5 μg·GBq-1. The research verifies that the tantalum target substrate can be used in 64Cu production, which avoids the process of electroplating gold and produces 64Cu more efficiently.

细胞凋亡是细胞死亡的一种重要形式,广泛存在于多种生理和病理过程中.细胞凋亡早期,胞膜内的磷脂酰乙醇胺(Phosphatidylethanolamine,PE)会翻转到细胞膜外表面,这一特征可以作为凋亡显像的靶点.耐久霉素(Duramycin)可与PE特异性结合,以放射性核素对耐久霉素进行标记后,可以利用核医学分子影像的手段,实现对细胞凋亡的活体无创检测.活体凋亡显像能在细胞水平上对肿瘤组织的改变进行早期、无创、动态的监测,从而准确判断肿瘤细胞对治疗药物的反应,有助于为临床个体化治疗方案的制定提供指导性意见.本文对放射性标记耐久霉素用于细胞凋亡显像的原理进行了总结和阐述,就近年来在凋亡显像示踪剂种类、制备及纯化方法、生物分布特征及其在肿瘤治疗早期疗效评估等方面的研究进展进行了综述,并对放射性核素标记耐久霉素的临床应用前景进行了展望.

Positron emission tomography (PET) has become the leading technology in the field of nuclear medicine.Currently,PET is widely used in tumor research,with high sensitivity,good resolution and so on.The construction of the 6aGe/ 68Ga generator has increased the application of 68Ga radiopharmaceuticals.The 68Ga radiopharmaceuticals are mainly applied on the imaging of oncological diseases,such as the targeting imaging of somatostatin receptor,human epidermal growth factor receptor,folate and so on.The potential for imaging of pulmonary and myocardial perfusion and ventilation as well as targeting imaging of inflammation,infection,have also been considered and fundamental exploration is ongoing.The application progress of 68Ga radiopharmaceuticals was reviewed,including production,receptors and derivatives,imaging of pre clinical developments on diagnosis.