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

Purpose Evaluation 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 poo...

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Bibliographic Details
Published in:European journal of nuclear medicine and molecular imaging 2015-06, Vol.42 (7), p.1106-1118
Main Authors: Vállez Garcia, David, de Vries, Erik F. J., Toyohara, Jun, Ishiwata, Kiichi, Hatano, Kentaro, Dierckx, Rudi A. J. O., Doorduin, Janine
Format: Article
Language:English
Subjects:
Animals
Cardiology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Encephalitis, Herpes Simplex - diagnostic imaging
Encephalitis, Herpes Simplex - genetics
Imaging
Imidazoles - chemical synthesis
Imidazoles - pharmacokinetics
Male
Medical imaging
Medicine
Medicine & Public Health
Neurological disorders
Nuclear Medicine
Oncology
Original
Original Article
Orthopedics
Positron-Emission Tomography
Protein expression
Proteins
Pyridines - chemical synthesis
Pyridines - pharmacokinetics
Radiology
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - pharmacokinetics
Rats
Rats, Wistar
Receptors, GABA-A - genetics
Receptors, GABA-A - metabolism
Tissue Distribution
Tomography
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Summary:Purpose Evaluation 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. Methods A 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. Results The biodistribution study showed significantly higher [ 11 C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum ( p  
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-015-3021-x