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

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

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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Acknowledgements

The technical support of Françoise Hinnen and Stéphane Demphel for the production of the radiotracers and of Benoit Jego and Karine Siquier for the PET studies is greatly appreciated. This study was funded in part by the EU - FP6 network EMIL (LSHC-CT-2004-503569), EU - FP6 network DiMI (LSHB-CT-2005-512146) and by the European Community (RATstream™ STREP, LSHM-CT-2007-037846). Nadja Van Camp is the recipient of a FWO fellowship from Belgium.

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Authors and Affiliations

  1. CEA, I2BM, SHFJ, Laboratoire d’Imagerie Moléculaire Expérimentale (LIME), 4 place Leclerc, 91400, Orsay, France

    Nadja Van Camp, Raphael Boisgard, Bertrand Kuhnast, Benoit Thézé, Thomas Viel, Fabien Chauveau, Frédéric Dollé & Bertrand Tavitian

  2. INSERM U803, Orsay, France

    Nadja Van Camp, Raphael Boisgard, Benoit Thézé, Thomas Viel, Fabien Chauveau & Bertrand Tavitian

  3. Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium

    Nadja Van Camp

  4. Radiopharmaceutical Research Institute, ANSTO, Lucas Heights, Australia

    Marie-Claude Grégoire & Andrew Katsifis

  5. CREATIS-LRMN; CNRS, UMR 5220, France; Inserm U630, Lyon, France

    Fabien Chauveau

  6. Faculty of Life Sciences, University of Manchester, M13 9PT, Manchester, UK

    Hervé Boutin

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  1. Nadja Van Camp
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Correspondence to Bertrand Tavitian.

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Van Camp, N., Boisgard, R., Kuhnast, B. et al. In vivo imaging of neuroinflammation: a comparative study between [18F]PBR111, [11C]CLINME and [11C]PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging 37, 962–972 (2010). https://doi.org/10.1007/s00259-009-1353-0

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  • DOI: https://doi.org/10.1007/s00259-009-1353-0

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