Mitochondria-Selective Reduction of 62Cu-Pyruvaldehyde Bis(N4-methylthiosemicarbazone)(62Cu-PTSM) in the Murine Brain; a Novel Radiopharmaceutical for Brain Positron Emission Tomography(PET) Imaging.

Abstract

The retention mechanism of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain was evaluated. For this purpose, stable Cu-PTSM was subjected to electron spin resonance spectrometry (ESR) and high performance liquid chromatography (HPLC) analysis to determine the valence state, coordination structure and tissue metabolism. In murine brain homogenate, ESR and HPLC analysis indicated the reduction and cleavage of Cu(II)-PTSM to Cu(I). This virtually irreversible reduction was specifically initiated by the mitochondrial enzymatic system in the murine brain.