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

Authors:
Julia Baguna Torres
Julia Baguna Torres
King's College London
London | United Kingdom
Zilin Yu
Zilin Yu
Peking University
China
Jayanta Bordoloi
Jayanta Bordoloi
King's College London
Kavitha Sunassee
Kavitha Sunassee
King's College London
David Smith
David Smith
University of Western Ontario
London | Canada
Claire Smith
Claire Smith
University of Southampton
United Kingdom
Oscar Chen
Oscar Chen
University of Oxford
Oxford | United States
Rupert Purchase
Rupert Purchase
rp@rupertpurchase.demon.co.uk

Biometals 2019 04 7;32(2):293-306. Epub 2019 Mar 7.

School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, SE1 7EH, UK.

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

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10534-019-00185-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437134PMC
April 2019
2 Reads
2.503 Impact Factor

Publication Analysis

Top Keywords

npc1 disease
12
emission tomography
12
positron emission
12
changes copper
8
mouse model
8
niemann-pick disease
8
enhanced retention
8
electronic autoradiography
8
copper trafficking
8
disease
5
npc1
5
cells allowing
4
dissociates rapidly
4
inside cells
4
rapidly inside
4
allowing monitoring
4
subsequent efflux
4
retention radioactivity
4
radioactivity observed
4
tissues enhanced
4

References

(Supplied by CrossRef)
Article in Metallomics
EM Andreozzi et al.
Metallomics 2017
Article in Metallomics
G Argüello et al.
Metallomics 2014
Article in Acta Neuropathol
I Auer et al.
Acta Neuropathol 1995
Article in J Nucl Med
JJ Bartnicka et al.
J Nucl Med 2018
Article in Am J Pathol
C Bhuvaneswaran et al.
Am J Pathol 1982
Article in J Clin Neurosci
BJ Connemann et al.
J Clin Neurosci 2012
Article in Science
JP Davies et al.
Science 2000
Article in J Alzheimers Dis
MT Fodero-Tavoletti et al.
J Alzheimers Dis 2010
Article in Front Physiol
YH Hung et al.
Front Physiol 2013
Article in Metallomics
YH Hung et al.
Metallomics 2014
Article in J Bacteriol
EH Kim et al.
J Bacteriol 2011

Similar Publications