In Vivo Imaging of Neuroinflammation in the Rodent Brain with [11C]SSR180575, a Novel Indoleacetamide Radioligand of the Translocator Protein (18 KDa)

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2010 Oct 12

PMID 20936410

Citations 29

Authors

Fabien Chauveau

Herve Boutin

Nadja Van Camp

Cyrille Thominiaux

Philippe Hantraye

Luc Rivron

Frank Marguet

Marie-Noelle Castel

Thomas Rooney

Jesus Benavides

Frederic Dolle

Bertrand Tavitian

Affiliations

Soon will be listed here.

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 (11)C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats.

Results: The image contrast and the binding of [(11)C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [(11)C]PK11195. Competition studies demonstrate that [(11)C]SSR180575 has high specific binding for the TSPO.

Conclusion: [(11)C]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.

Citing Articles

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A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression.

Conte M, De Feo M, Corica F, Gorica J, Sidrak M, De Cristofaro F Biomolecules. 2023; 13(4).

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References

Homes T, Mattner F, Keller P, Katsifis A . Synthesis and in vitro binding of N,N-dialkyl-2-phenylindol-3-yl-glyoxylamides for the peripheral benzodiazepine binding sites. Bioorg Med Chem. 2006; 14(11):3938-46. DOI: 10.1016/j.bmc.2006.01.039. View

Venneti S, Lopresti B, Wiley C . The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol. 2006; 80(6):308-22. PMC: 1849976. DOI: 10.1016/j.pneurobio.2006.10.002. View

Vin V, Leducq N, Bono F, Herbert J . Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand. Biochem Biophys Res Commun. 2003; 310(3):785-90. DOI: 10.1016/j.bbrc.2003.09.079. View

Veenman L, Gavish M . The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development. Pharmacol Ther. 2005; 110(3):503-24. DOI: 10.1016/j.pharmthera.2005.09.007. View

Leducq N, Bono F, Sulpice T, Vin V, Janiak P, Le Fur G . Role of peripheral benzodiazepine receptors in mitochondrial, cellular, and cardiac damage induced by oxidative stress and ischemia-reperfusion. J Pharmacol Exp Ther. 2003; 306(3):828-37. DOI: 10.1124/jpet.103.052068. View

Van Camp N, Boisgard R, Kuhnast B, Theze B, Viel T, Gregoire M . In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [ (11)C]CLINME and [ (11)C]PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging. 2010; 37(5):962-72. DOI: 10.1007/s00259-009-1353-0. View

Ferzaz B, Brault E, Bourliaud G, Robert J, Poughon G, Claustre Y . SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair. J Pharmacol Exp Ther. 2002; 301(3):1067-78. DOI: 10.1124/jpet.301.3.1067. View

Benavides J, Fage D, Carter C, Scatton B . Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage. Brain Res. 1987; 421(1-2):167-72. DOI: 10.1016/0006-8993(87)91287-x. View

Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B . Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008; 35(12):2304-19. DOI: 10.1007/s00259-008-0908-9. View

10.

Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A . Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009; 50(3):468-76. DOI: 10.2967/jnumed.108.058669. View

11.

Boutin H, Chauveau F, Thominiaux C, Kuhnast B, Gregoire M, Jan S . In vivo imaging of brain lesions with [(11)C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors. Glia. 2007; 55(14):1459-68. DOI: 10.1002/glia.20562. View

12.

Boutin H, Chauveau F, Thominiaux C, Gregoire M, James M, Trebossen R . 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med. 2007; 48(4):573-81. DOI: 10.2967/jnumed.106.036764. View