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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.05.2010 | Original Article

In vivo imaging of neuroinflammation: a comparative study between [¹⁸F]PBR111, [¹¹C]CLINME and [¹¹C]PK11195 in an acute rodent model

verfasst von: Nadja Van Camp, Raphael Boisgard, Bertrand Kuhnast, Benoit Thézé, Thomas Viel, Marie-Claude Grégoire, Fabien Chauveau, Hervé Boutin, Andrew Katsifis, Frédéric Dollé, Bertrand Tavitian

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2010

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Abstract

Purpose

The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [¹⁸F]PBR111 in a rodent model of acute inflammation and compare it with [¹¹C]CLINME, an ¹¹C-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [¹¹C]PK11195.

Methods

We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging.

Results

We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [¹⁸F]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [¹⁸F]PBR111 administration, induces a rapid and complete displacement of [¹⁸F]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [¹¹C]PK11195.

Conclusion

[¹⁸F]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of ¹⁸F over ¹¹C, these results support [¹⁸F]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging.

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Titel: In vivo imaging of neuroinflammation: a comparative study between [18F]PBR111, [11C]CLINME and [11C]PK11195 in an acute rodent model
verfasst von: Nadja Van Camp
Raphael Boisgard
Bertrand Kuhnast
Benoit Thézé
Thomas Viel
Marie-Claude Grégoire
Fabien Chauveau
Hervé Boutin
Andrew Katsifis
Frédéric Dollé
Bertrand Tavitian
Publikationsdatum: 01.05.2010
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2010
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1353-0

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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