医用^(68)Ge-^(68)Ga发生器研究进展

The Current Development Status of^(68)Ge-^(68) Ga Generators for Medical Use

^(68)Ga是最早用于正电子发射计算机断层显像诊断疾病的放射性核素之一,主要通过^(68)Ge-^(68)Ga发生器制备。早期^(68)Ge-^(68)Ga发生器制备的^(68)Ga以络合物形式存在,如^(68)Ga-EDTA,由于EDTA络合能力较强,^(68)Ga-EDTA络合物不易转变为其他^(68)Ga化合物,因此^(68)Ga显像剂的发展受到限制。直到20世纪末俄罗斯科学家才研制出可以获得^(68)Ga Cl 3溶液的^(68)Ge-^(68)Ga发生器。随后,多款^(68)Ge-^(68)Ga发生器陆续供应市场,快速推动了新型^(68)Ga显像剂的研发进程。但是,从^(68)Ge-^(68)Ga发生器中淋洗出的^(68)Ga洗脱液存在^(68)Ge漏穿、洗脱液体积大、氢离子浓度高,以及金属阳离子杂质可能在标记反应中与^(68)Ga竞争等问题。研制出具有优异吸附及解吸性能的新型柱吸附剂是解决上述问题的关键。因此,本研究结合国内外^(68)Ge-^(68)Ga发生器的发展历程,总结了近年来发生器的现状、存在的问题,以及新型柱吸附剂的研究进展,为^(68)Ga核素制备以及发生器柱吸附剂的研究提供参考。

^(68)Ga,mainly prepared by^(68)Ge-^(68)Ga generator,is one of the radionuclides used in positron emission computed tomography(PET)for diagnosis of disease at the earliest.The early^(68)Ge-^(68)Ga generators could only produce^(68)Ga complexes such as^(68)Ga-EDTA,rather than^(68)Ga Cl 3.Due to the strong complexing ability of EDTA,^(68)Ga-EDTA is hardly transformed into other^(68)Ga labeling compounds,which hampers the development of^(68)Ga imaging agents.Until the end of the 20th century,Russian cyclotron company scientists made pioneering achievements.Not only did they finish the commercialization of^(68)Ge-^(68)Ga generator,but they produced the cationic^(68)Ga 3+.Subsequently,many^(68)Ge-^(68)Ga generators have been supplied to global markets,paving the way for the development of the novel^(68)Ga imaging agents.It is worth noting that the quality and characteristics of^(68)Ga eluate have an important effect on the efficiency of^(68)Ga-labeling chemistry,including in eluate volume,^(68)Ga radioactivity concentration,HCl eluent molarity,and content of metal cationic impurities.At present,there are some drawbacks in the available^(68)Ge-^(68)Ga generators,for example,^(68)Ge breakthrough,large^(68)Ga eluate volume,high concentration of hydrogen ions,and cationic metal ion impurities that might compete with^(68)Ga in the complexation reaction.To overcome the drawbacks,several measures have been taken to concentrate and purify^(68)Ga eluate prior to the labeling synthesis,such as anion exchange chromatography,cation exchange chromatography or their combination.However,the development of novel^(68)Ge adsorbents with excellent adsorption performance can fundamentally solve the problems,perhaps.At present,many novel adsorbents show the excellent performance for^(68)Ge,for example,nano-materials,composite materials,and inorganic oxides.Given the above,this paper reviews the present situation of^(68)Ge-^(68)Ga generators,existing problems,and research progress of novel column adsorbents in recent years according to the development history of^(68)Ge-^(68)Ga generators both at home and abroad,which will provide a reference for the production of^(68)Ga and the study of novel adsorbents.