Imaging of changes in copper trafficking and redistribution in a mouse model of Niemann-Pick C disease using positron emission tomography

摘要

Niemann-Pick C disease (NPC) is an autosomal recessive lysosomal storage disorder resulting from mutations in the NPC1 (95% of cases) or NPC2 genes. Disturbance of copper homeostasis has been reported in NPC1 disease. In this study we have used whole-body positron emission tomography (PET) and brain electronic autoradiography with copper-64 (Cu-64), in the form of the copper(II) bis(thiosemicarbazonato) complex Cu-64-GTSM, to image short-term changes in copper trafficking after intravenous injection in a transgenic mouse model of NPC1 disease. Cu-64-GTSM is taken up in all tissues and dissociates rapidly inside cells, allowing monitoring of the subsequent efflux and redistribution of Cu-64 from all tissues. Significantly enhanced retention of Cu-64 radioactivity was observed in brain, lungs and blood at 15h post-injection in symptomatic Npc1(-/-) transgenic mice compared to wildtype controls. The enhanced retention of Cu-64 in brain was confirmed by electronic autoradiography, particularly in the midbrain, thalamus, medulla and pons regions. Positron emission tomography imaging with Cu-64 in selected chemical forms could be a useful diagnostic and research tool for the management and understanding of NPC1 disease.