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Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

An Erratum to this article was published on 10 July 2008

Abstract

Background

The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders.

Purpose

To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4′iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion.

Methods

Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5–6/group) were i.v. injected with [125I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([3H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections.

Results

In the control group, [125I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p < 0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation.

Conclusion

These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation.

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Acknowledgements

All studies were conducted according to the French legislation and European directives. This work was financially supported in part by the EC-FP6-project DiMI, LSHB-CT-2005-512146.

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Authors and Affiliations

  1. Inserm, U930, Tours, 37000, France

    Nicolas Arlicot, Lucette Garreau, Jackie Vergote, Stéphanie Duval, Sylvie Bodard, Denis Guilloteau & Sylvie Chalon

  2. Université François Rabelais, Tours, 37000, France

    Nicolas Arlicot, Lucette Garreau, Jackie Vergote, Stéphanie Duval, Sylvie Bodard, Denis Guilloteau & Sylvie Chalon

  3. CHRU de Tours, Tours, 37000, France

    Nicolas Arlicot, Stéphanie Duval, Denis Guilloteau & Sylvie Chalon

  4. Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, Australia

    Andrew Katsifis & Filomena Mattner

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Correspondence to Sylvie Chalon.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00259-008-0882-2

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Arlicot, N., Katsifis, A., Garreau, L. et al. Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation. Eur J Nucl Med Mol Imaging 35, 2203–2211 (2008). https://doi.org/10.1007/s00259-008-0834-x

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