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内容記述 |
[Cu]Cu-diacetyl-bis(-methylthiosemicarbazone) ([Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of Cu and ATSM is important. In this study, we conducted coordination chemistry studies on metal-ATSM complexes. First, the effects of nonradioactive metal ions (Cu, Ni, Zn, and Fe) on the formation of [Cu]Cu-ATSM were evaluated. When the amount of Cu or Ni added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn or Fe were added to the ATSM. Second, these metals were reacted with ATSM, and chelate formation was measured using ultraviolet-visible (UV-Vis) absorption spectra. UV-Vis spectra showed a rapid formation of Cu and the ATSM complex upon mixing. The rate of chelate formation by Ni and ATSM was lower than that by Cu-ATSM. Zn and Fe showed much slower reactions with the ATSM than Ni. Trace amounts of Ni, Zn, and Fe showed little effect on [Cu]Cu-ATSM' quality, while the concentration of impurity Cu must be controlled. These results can provide process management tools for radiopharmaceuticals. |
