Evaluation of [C-11]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

David Vállez Garcia, Erik F. J. de Vries, Jun Toyohara, Kiichi Ishiwata, Kentaro Hatano, Rudi A. J. O. Dierckx, Janine Doorduin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSE: Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [11C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [11C]CB184 was evaluated as a potentially more sensitive PET tracer.

METHODS: A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [11C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [11C]CB184 and [11C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis.

RESULTS: The biodistribution study showed significantly higher [11C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r2 = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [11C]CB184 uptake in the whole brain. Both, [11C]CB184 and [11C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BPND) was not significantly different between the HSE rats and the control rats. In HSE rats BPND for [11C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [11C]PK11195 was only detected in the medulla.

CONCLUSION: [11C]CB184 showed nonspecific binding to healthy tissue comparable to that observed for [11C]PK11195, but it displayed significantly higher specific binding in those brain regions affected by the HSE. Our results suggest that [11C]CB184 PET is a good alternative for imaging of neuroinflammatory processes.

Original languageEnglish
Pages (from-to)1106-1118
Number of pages13
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume42
Issue number7
DOIs
Publication statusPublished - Jun-2015

Keywords

  • PET
  • TSPO
  • PBR
  • Neuroinflammation
  • Rat
  • PERIPHERAL BENZODIAZEPINE-RECEPTOR
  • PROTEIN 18 KDA
  • POSITRON-EMISSION-TOMOGRAPHY
  • IN-VIVO
  • SIMPLEX-VIRUS
  • PET RADIOLIGAND
  • BINDING-SITES
  • BRAIN
  • MICROGLIA
  • DISEASE

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