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|Title:||In vivo imaging of neuroinflammation: a comparative study between [F-18]PBR111, [C-11]CLINME and [C-11]PK11195 in an acute rodent model.|
|Authors:||Van Camp, N|
Grégoire, M C
|Keywords:||Positron computed tomography|
Central nervous system
|Citation:||Van Camp, N., Boisgard, R., Kuhnast, B., Thézé, B., Viel, T., Grégoire, M. C., Chauveau, F., Boutin, H., Katsifis, A., Dolle, F., & Tavitian, B. (2010). In vivo imaging of neuroinflammation: a comparative study between [F-18]PBR111, [C-11]CLINME and [C-11]PK11195 in an acute rodent model. European Journal of Nuclear Medicine and Molecular Imaging, 37(5), 962-972. doi:10.1007/s00259-009-1353-0|
|Abstract:||The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [F-18]PBR111 in a rodent model of acute inflammation and compare it with [C-11]CLINME, an C-11-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [C-11]PK11195. We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [F-18]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [F-18]PBR111 administration, induces a rapid and complete displacement of [F-18]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [C-11]PK11195. [F-18]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of F-18 over C-11, these results support [F-18]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging. © 2010, Springer.|
|Gov't Doc #:||5687|
|Appears in Collections:||Journal Articles|
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