Evaluation of [11C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis

Doorduin, Janine; Klein, Hans C.; de Jong, Johan R.; Dierckx, Rudi A.; de Vries, Erik F.J.

doi:10.1016/j.nucmedbio.2009.09.002

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 1 , Pages 9-15, January 2010

Evaluation of [¹¹C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis

Janine Doorduin
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
- Corresponding author. Tel.: +31 50 3613311; fax: +31 50 3611687.
Hans C. Klein
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
- University Center of Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Johan R. de Jong
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Rudi A. Dierckx
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Erik F.J. de Vries
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands

Received 30 July 2009; received in revised form 2 September 2009; accepted 19 September 2009. published online 23 October 2009.

Abstract

Introduction

Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [¹¹C]-PK11195 can be used to study neuroinflammation in these disorders. However, [¹¹C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [¹¹C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis.

Methods

Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [¹¹C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake.

Results

In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [¹¹C]-DAA1106 was found in almost all examined brain areas (24–71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [¹¹C]-DAA1106 uptake in HSE rats (54–84%; P<.001). The plasma and brain time–activity curves showed rapid uptake of [¹¹C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to a two-tissue compartment model.

Conclusions

[¹¹C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [¹¹C]-DAA1106 PET. Quantification of the uptake of [¹¹C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.

Keywords: Positron emission tomography, Neuroinflammation, Microglia, Herpes viruses, [¹¹C]-DAA1106, [¹¹C]-PK11195, TSPO