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Published in: European Journal of Nuclear Medicine and Molecular Imaging 8/2011

01-08-2011 | Original Article

Evaluation of [123I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation

Authors: Filomena Mattner, David Linares Bandin, Maria Staykova, Paula Berghofer, Marie Claude Gregoire, Patrice Ballantyne, Mitchell Quinlivan, Susan Fordham, Tien Pham, David O. Willenborg, Andrew Katsifis

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2011

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Abstract

Purpose

The purpose of this study was to assess the feasibility and sensitivity of the high-affinity translocator protein (TSPO) ligand [123I]-CLINDE in imaging TSPO changes in vivo and characterise and compare astroglial and TSPO changes in the cuprizone model of demyelination and remyelination in C57BL/6 mice.

Methods

C57BL/6 mice were fed with cuprizone for 4 weeks to induce demyelination followed by 2–4 weeks of standard diet (remyelination). Groups of mice were followed by in vivo single photon emission computed tomography (SPECT)/CT imaging using [123I]-CLINDE and uptake correlated with biodistribution, autoradiography, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR).

Results

The uptake of [123I]-CLINDE in the brain as measured by SPECT imaging over the course of treatment reflects the extent of the physiological response, with significant increases observed during demyelination followed by a decrease in uptake during remyelination. This was confirmed by autoradiography and biodistribution studies. A positive correlation between TSPO expression and astrogliosis was found and both activated astrocytes and microglial cells expressed TSPO. [123I]-CLINDE uptake reflects astrogliosis in brain structures such as corpus callosum, caudate putamen, medium septum and olfactory tubercle as confirmed by both in vitro and in vivo results.

Conclusion

The dynamics in the cuprizone-induced astroglial and TSPO changes, observed by SPECT imaging, were confirmed by immunofluorescence, RT-PCR and autoradiography. The highly specific TSPO radioiodinated ligand CLINDE can be used as an in vivo marker for early detection and monitoring of a variety of neuropathological conditions using noninvasive brain imaging techniques.
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Metadata
Title
Evaluation of [123I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation
Authors
Filomena Mattner
David Linares Bandin
Maria Staykova
Paula Berghofer
Marie Claude Gregoire
Patrice Ballantyne
Mitchell Quinlivan
Susan Fordham
Tien Pham
David O. Willenborg
Andrew Katsifis
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-011-1784-2

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