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

Julia Baguña Torres, Zilin Yu, Jayanta Bordoloi, Kavitha Sunassee, David Smith, Claire Smith, Oscar Chen, Rupert Purchase, Karin Tuschl, John Spencer, Frances Platt, Philip J. Blower

Research output: Contribution to journalArticlepeer-review

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Abstract

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 imageshort-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 subsequentefflux 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 towildtype controls. The enhanced retention of 64Cu in brain was confirmed by electronic autoradiography, particularly in the midbrain, thalamus, medulla and pons regions. PET imaging with 64Cu in selected chemical forms could be a useful diagnostic and research tool for the management and understanding of NPC1 disease.
Original languageEnglish
Pages (from-to)293-306
Number of pages14
JournalBiometals
Volume32
Issue number2
Early online date7 Mar 2019
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • Autoradiography
  • Copper dyshomeostasis
  • Copper-64
  • Niemann-Pick C
  • Positron emission tomography

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