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

The model complex [Cu-64((S)-p-NH2-Bn-NOTA)](-) ([Cu-64]1) was used to study the isomerism of [Cu-64-NOTA-Bn]-labeled radiotracers. Two complex isomers [Cu-64]1a and [Cu-64]1b, which were formed at a ratio of 1:9 during the complexation of [Cu-64]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 degrees 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.