Abstract
Purpose
Neuroinflammation is involved in neurological disorders through the activation of microglial cells. Imaging of neuroinflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive biomarker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuroprotective effects.
Methods
Here we report the radiolabelling of SSR180575 with 11C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats.
Results
The image contrast and the binding of [11C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [11C]PK11195. Competition studies demonstrate that [11C]SSR180575 has high specific binding for the TSPO.
Conclusion
[11C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuroinflammation in animal models and in the clinic.
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Acknowledgements
The authors thank Yoann Fontyn and Vincent Brulon from CEA for their help during imaging experiments and Dominique Briet from Sanofi-Aventis for her help with the autoradiographic experiments. H. Boutin and C. Thominiaux were supported by a CEA/Sanofi-Aventis fellowship. This work was supported by the EC-FP6 Networks of Excellence European Molecular Imaging Laboratory (EMIL) (LSH-2004-503569) and Diagnostic Molecular Imaging (DiMI) (LSHB-CT-2005-512146).
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Fabien Chauveau and Hervé Boutin contributed equally to this work.
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Chauveau, F., Boutin, H., Van Camp, N. et al. In vivo imaging of neuroinflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa). Eur J Nucl Med Mol Imaging 38, 509–514 (2011). https://doi.org/10.1007/s00259-010-1628-5
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DOI: https://doi.org/10.1007/s00259-010-1628-5