Isomerism of [64Cu-NOTA-Bn]-Labeled Radiotracers: Separation of Two Complex Isomers and Determination of Their Interconversion Energy Barrier Using Ion Pair Chromatography

The model complex [64Cu((S)-p-NH2-Bn-NOTA)]− ([64Cu]1) was used to study the isomerism of [64Cu-NOTA-Bn]-labeled radiotracers. Two complex isomers [64Cu]1a and [64Cu]1b, which were formed at a ratio of 1:9 during the complexation of [64Cu]Cu2+ with (S)-p-NH2-Bn-NOTA, were separated using ion pair chromatography. To study the interconversion, the nonradioactive complex isomers Cu1a and Cu1b were separated and thermally treated at 90 °C in both ammonium acetate solution and deionized water. A faster interconversion rate was observed for both isomers with lower concentrations of ammonium ions. At the end of reaction, the thermodynamic Cu1a to Cu1b equilibrium ratio was 6:94. The particular energy barriers of the interconversion for Cu1a and Cu1b were 130 kJ mol−1 and 140 kJ mol−1. Spectrophotometric measurements with Cu1a and Cu1b revealed two isomers adopting different geometrical configurations.