Please use this identifier to cite or link to this item: https://apo.ansto.gov.au/dspace/handle/10238/9117
Title: In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors
Authors: Boutin, H
Chauveau, F
Thominiaux, C
Kuhnast, B
Gregoire, MC
Jan, S
Trebossen, R
Dolle, F
Tavitian, B
Mattner, F
Katsifis, A
Keywords: Positron computed tomography
Inflammation
Receptors
Ligands
Brain
Rats
Autoradiography
Images
Issue Date: 6-Aug-2007
Publisher: John Wiley and Sons
Citation: Boutin, H., Chauveau, F., Thominiaux, C., Kuhnast, B., Gregoire, M. C., Jan, S., Trebossen, C., Traitian, B., Mattner, F., & Katsifis., A. (2007). In vivo imaging of brain lesions with [11C] CLINME, a new PET radioligand of peripheral benzodiazepine receptors. Glia, 55(14), 1459-1468. doi:10.1002/glia.20562
Abstract: The peripheral benzodiazepine receptor (PBR) is expressed by microglial cells in many neuropathologies involving neuroinflammation. PK11195, the reference compound for PBR, is used for positron emission tomography (PET) imaging but has a limited capacity to quantify PBR expression. Here we describe the new PBR ligand CLINME as an alternative to PK11195. In vitro and in vivo imaging properties of [11C]CLINME were studied in a rat model of local acute neuroinflammation, and compared with the reference compound [11C]PK11195, using autoradiography and PET imaging. Immunohistochemistry study was performed to validate the imaging data. [11C]CLINME exhibited a higher contrast between the PBR-expressing lesion site and the intact side of the same rat brain than [11C]PK11195 (2.14 ± 0.09 vs. 1.62 ± 0.05 fold increase, respectively). The difference was due to a lower uptake for [11C]CLINME than for [11C]PK11195 in the non-inflammatory part of the brain in which PBR was not expressed, while uptake levels in the lesion were similar for both tracers. Tracer localization correlated well with that of activated microglial cells, demonstrated by immunohistochemistry and PBR expression detected by autoradiography. Modeling using the simplified tissue reference model showed that R1 was similar for both ligands (R1 ∼ 1), with [11C]CLINME exhibiting a higher binding potential than [11C]PK11195 (1.07 ± 0.30 vs. 0.66 ± 0.15). The results show that [11C]CLINME performs better than [11C]PK11195 in this model. Further studies of this new compound should be carried out to better define its capacity to overcome the limitations of [11C]PK11195 for PBR PET imaging. © 2007 Wiley-Liss, Inc.
Gov't Doc #: 8686
URI: http://doi.org/10.1002/glia.20562
http://apo.ansto.gov.au/dspace/handle/10238/9117
ISSN: 1098-1136
Appears in Collections:Journal Articles

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