• David Vállez Garcia, Erik F J de Vries, Jun Toyohara, Kiichi Ishiwata, Kentaro Hatano, Rudi A J O Dierckx, and 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, d.vallez-garcia@umcg.nl.
• Eur. J. Nucl. Med. Mol. Imaging. 2015 Jun 1; 42 (7): 1106-18.

PurposeEvaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [(11)C]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, [(11)C]CB184 was evaluated as a potentially more sensitive PET tracer.MethodsA model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [(11)C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [(11)C]CB184 and [(11)C]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.ResultsThe biodistribution study showed significantly higher [(11)C]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, r (2) = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [(11)C]CB184 uptake in the whole brain. Both, [(11)C]CB184 and [(11)C]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 [(11)C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [(11)C]PK11195 was only detected in the medulla.Conclusion[(11)C]CB184 showed nonspecific binding to healthy tissue comparable to that observed for [(11)C]PK11195, but it displayed significantly higher specific binding in those brain regions affected by the HSE. Our results suggest that [(11)C]CB184 PET is a good alternative for imaging of neuroinflammatory processes.

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