Matsumoto K, Fujibayashi Y, Konishi J, Yokoyama A
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Radioisotopes. 1990 Nov;39(11):482-6. doi: 10.3769/radioisotopes.39.11_482.
The newly developed 62Zn/62Cu generator system has made available the production of the short-lived 62Cu (T1/2 = 9.8 min) positron radionuclide, eluted as 62Cu-glycine. In the search for 62Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62Zn/62Cu generator eluate, the 62Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62Cu-DDC and 62Cu-DmDC were extremely high (non-detectable 62Cu-glycine) and both chelates were more lipophilic than 62Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62Cu-DDC and 62Cu-DmDC indicated a brain accumulation of 2.8 and 5.3 times higher than 62Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62Cu-DDC and 62Cu-DmDC might be due to their stable, neutral and lipophylic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62Cu-labeled compounds using the 62Zn/62Cu generator system based on the ligand exchange reaction with 62Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62Cu positron radiopharmaceuticals can be recalled.
新开发的62Zn/62Cu发生器系统可用于生产短寿命的62Cu（半衰期T1/2 = 9.8分钟）正电子放射性核素，以62Cu-甘氨酸形式洗脱。在寻找用于正电子CT（PET）脑诊断研究的62Cu标记放射性药物时，基于其铜螯合能力及其铜螯合物的中性亲脂特性，选择了两种配体N，N-二乙基和N，N-二甲基二硫代氨基甲酸（DDC和DmDC）。在本工作中，用非放射性Cu-甘氨酸进行的体外研究表明，基于配体交换反应，两种配体都能轻松形成稳定的中性Cu-DDC和Cu-DmDC螯合物（1:2金属-配体络合物）。然后，使用62Zn/62Cu发生器洗脱液62Cu-甘氨酸对DDC和DmDC进行放射性标记。随后的HPLC分析表明配体交换反应进行迅速；62Cu-DDC和62Cu-DmDC的放射化学纯度极高（未检测到62Cu-甘氨酸），且两种螯合物都比62Cu-甘氨酸更具亲脂性。两种放射性标记化合物62Cu-DDC和62Cu-DmDC在小鼠体内的生物分布表明，注射后15分钟，它们在脑中的蓄积量分别比62Cu-甘氨酸高2.8倍和5.3倍。观察到62Cu-DDC和62Cu-DmDC在脑中的蓄积可能归因于它们稳定、中性和亲脂的特性；甲基化侧链的存在增强了后者。收集到的结果表明，基于与62Cu-甘氨酸洗脱液的配体交换反应，二硫代氨基甲酸衍生物可用于使用62Zn/62Cu发生器系统生产新的62Cu标记化合物。可以回顾对用于开发新的发生器生产的62Cu正电子放射性药物的铜二硫代氨基甲酸衍生物的进一步研究。
