In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors

Faculty of Life Sciences, University of Manchester, United Kingdom
Glia (Impact Factor: 6.03). 11/2007; 55(14):1459 - 1468. DOI: 10.1002/glia.20562


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.

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Available from: Herve Boutin, Jul 14, 2014
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    • "probes designed for binding to inflammatory processes, such as [ 11 C]PK11195, [ 11 C]DAA1106, [ 11 C]DPA-713, and [ 11 C]CLINME have been widely used for studying brain infl ammation [60] [61] [62] [63] . The principal immune cells in the central nervous system, microglia, are activated in response to inflammatory processes in the brain [64] . "
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    Neuroscience Bulletin 10/2014; 30(5):812-22. DOI:10.1007/s12264-014-1471-y · 2.51 Impact Factor
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    • "They have been used to explore TSPO distribution and function in various tissues and pathologies becoming useful in mapping the " peripheral binding site " in almost every tissue examined. More recently, new structurally diverse TSPO drug ligands have been developed and used for functional and imaging studies such as 2-phenylindole-3-acetamides (e.g., FGIN-1) [22], phenoxyarylacetamides (e.g., DAA1106) [23] [24], imidazo[1,2-a] pyridines (e.g., CLINME) [23] [25], and pyrazolopyrimidines (e.g., DPA- 713) [23] [24]. To our knowledge, none of all the above cited TSPO drug ligands contain organic functions such as amino-, hydroxy-and carboxylic-groups potentially useful for their further conjugation with diagnostic-or with nanovector-imaging agents. "
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    • "Numerous radiolabeled TSPO ligands have been developed and evaluated in animal models of disease and in humans; of these [11C]PK11195 is the ligand most extensively studied [10], [11]. Several other ligands with improved properties (e.g. higher affinity, lower lipophilicity) have been described including [11C]vinpocetin [12], [18F]FMDAA1106, [18F]FEDAA1106 [13], [123I]CLINDE [14], [11C]CLINME [15], [18F]FEPPA or [18F]PBR28 [16], [11C]DAC [17], and [11C]DAA1106 [18]. The pyrazolopyrimidine [18F]DPA-714 was introduced in 2008 by James and colleagues as a highly specific new radioligand for TSPO with improved imaging properties over [11C]PK11195 [19]. "
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