Trace Metal Impurities Effects on the Formation of [ 64 Cu]Cu-diacetyl-bis( N 4 -methylthiosemicarbazone) ([ 64 Cu]Cu-ATSM).

[ 64 Cu]Cu-diacetyl-bis( N 4 -methylthiosemicarbazone) ([ 64 Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [ 64 Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of 64 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 2+ , Ni 2+ , Zn 2+ , and Fe 2+ ) on the formation of [ 64 Cu]Cu-ATSM were evaluated. When the amount of Cu 2+ or Ni 2+ added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [ 64 Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn 2+ or Fe 2+ 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 2+ and the ATSM complex upon mixing. The rate of chelate formation by Ni 2+ and ATSM was lower than that by Cu-ATSM. Zn 2+ and Fe 2+ showed much slower reactions with the ATSM than Ni 2+ . Trace amounts of Ni 2+ , Zn 2+ , and Fe 2+ showed little effect on [ 64 Cu]Cu-ATSM' quality, while the concentration of impurity Cu 2+ must be controlled. These results can provide process management tools for radiopharmaceuticals.