Zentralklinik Bad Berka, Department of Nuclear Medicine/PET Center, 99437 Bad Berka, Germany.
Bioconjug Chem. 2012 Aug 15;23(8):1712-7. doi: 10.1021/bc300103t. Epub 2012 Jul 19.
A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals. For the (68)Ga generator eluate concentration step, commercially available cation-exchange cartridges and (68)Ga generators were used. The (68)Ga generator eluate was collected by use of a strong cation exchange cartridge. 98% of the total activity of (68)Ga was then eluted from the cation exchange cartridge with 0.5 mL of 5 M NaCl solution containing a small amount of 5.5 M HCl. After buffering with ammonium acetate, the eluate was used directly for radiolabeling of DOTATOC and DOTATATE. The (68)Ga-labeled peptides were obtained in higher radiochemical purity compared to other commonly used procedures, with radiochemical yields greater than 80%. The presence of (68)Ge could not be detected in the final product. The new method obviates the need for organic solvents, which eliminates the required quality control of the final product by gas chromatography, thereby reducing postsynthesis analytical effort significantly. The (68)Ga-labeled products were used directly, with no subsequent purification steps, such as solid-phase extraction. The NaCl method was further evaluated using an automated fluid handling system and it routinely facilitates radiochemical yields in excess of 65% in less than 15 min, with radiochemical purity consistently greater than 99% for the preparation of (68)Ga-DOTATOC.
一种简单的基于氯化钠（NaCl）的（68）Ga 洗脱液浓度和标记方法，能够快速、高效地标记 DOTA 结合的肽，具有高放射化学纯度。该方法使用相对较少的试剂，且步骤最少。它特别适合于临床放射性药物的常规自动化合成。对于（68）Ga 发生器洗脱液浓度步骤，使用了市售的阳离子交换柱和（68）Ga 发生器。（68）Ga 发生器洗脱液通过使用强阳离子交换柱收集。然后，用含有少量 5.5 M HCl 的 0.5 mL 5 M NaCl 溶液从阳离子交换柱上洗脱 98%的（68）Ga 总活度。用乙酸铵缓冲后，直接用洗脱液标记 DOTATOC 和 DOTATATE。与其他常用方法相比，（68）Ga 标记的肽具有更高的放射化学纯度，放射化学收率大于 80%。最终产物中未检测到（68）Ge 的存在。新方法避免了有机溶剂的使用，从而消除了对最终产物进行气相色谱质量控制的需要，从而大大减少了合成后的分析工作量。（68）Ga 标记的产物无需进一步纯化步骤，如固相萃取，直接使用。NaCl 法进一步用自动化流体处理系统进行了评估，它通常可以在不到 15 分钟内以超过 65%的放射化学收率促进（68）Ga-DOTATOC 的制备，且放射化学纯度始终大于 99%。
