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 (64Cu), in the form of the copper(II) bis(thiosemicarbazonato) complex 64Cu-GTSM, to image short-term changes in copper trafficking after intravenous injection in a transgenic mouse model of NPC1 disease. 64Cu-GTSM is taken up in all tissues and dissociates rapidly inside cells, allowing monitoring of the subsequent efflux and redistribution of 64Cu from all tissues. Significantly enhanced retention of 64Cu radioactivity was observed in brain, lungs and blood at 15 h post-injection in symptomatic Npc1-/- transgenic mice compared to wildtype controls. The enhanced retention of 64Cu in brain was confirmed by electronic autoradiography, particularly in the midbrain, thalamus, medulla and pons regions. Positron emission tomography imaging with 64Cu in selected chemical forms could be a useful diagnostic and research tool for the management and understanding of NPC1 disease.

中文翻译：

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使用正电子发射断层扫描对尼曼-匹克 C 病小鼠模型中铜运输和再分布的变化进行成像。


尼曼-匹克 C 病 (NPC) 是一种常染色体隐性遗传性溶酶体贮积症，由 NPC1（95% 的病例）或 NPC2 基因突变引起。据报道，NPC1 疾病中存在铜稳态紊乱。在本研究中，我们使用全身正电子发射断层扫描 (PET) 和脑电子放射自显影技术，以铜 (II) 双（氨基硫脲）络合物 64Cu-GTSM 形式的铜 64 (64Cu) 进行短期成像NPC1 疾病转基因小鼠模型静脉注射后铜转运的变化。 64Cu-GTSM 被所有组织吸收并在细胞内快速解离，从而可以监测 64Cu 从所有组织的后续流出和重新分配。与野生型对照相比，在有症状的 Npc1-/- 转基因小鼠中注射 15 小时后，在脑、肺和血液中观察到 64Cu 放射性的保留显着增强。电子放射自显影证实了 64Cu 在大脑中的保留增强，特别是在中脑、丘脑、延髓和脑桥区域。使用选定化学形式的 64Cu 进行正电子发射断层扫描成像可能是管理和了解 NPC1 疾病的有用诊断和研究工具。