PT  - JOURNAL ARTICLE
AU  - Hervé Boutin
AU  - Fabien Chauveau
AU  - Cyrille Thominiaux
AU  - Marie-Claude Grégoire
AU  - Michelle L. James
AU  - Régine Trebossen
AU  - Philippe Hantraye
AU  - Frédéric Dollé
AU  - Bertrand Tavitian
AU  - Michael Kassiou
TI  - <sup>11</sup>C-DPA-713: A Novel Peripheral Benzodiazepine Receptor PET Ligand for In Vivo Imaging of Neuroinflammation
AID  - 10.2967/jnumed.106.036764
DP  - 2007 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 573--581
VI  - 48
IP  - 4
4099  - http://jnm.snmjournals.org/content/48/4/573.short
4100  - http://jnm.snmjournals.org/content/48/4/573.full
SO  - J Nucl Med2007 Apr 01; 48
AB  - The induction of neuroinflammatory processes, characterized by upregulation of the peripheral benzodiazepine receptor (PBR) expressed by microglial cells, is well correlated with neurodegenerative diseases and with acute neuronal loss. The continually increasing incidence of neurodegenerative diseases in developed countries has become a major health problem, for which the development of diagnostic and follow-up tools is required. Here we investigated a new PBR ligand suitable for PET to monitor neuroinflammatory processes as an indirect hallmark of neurodegeneration. Methods: We compared PK11195, the reference compound for PBR binding sites, with the new ligand DPA-713 (N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide), using a small-animal dedicated PET camera in a model of neuroinflammation in rats. Seven days after intrastriatal injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), a PET scan was performed using 11C-PK11195 or 11C-DPA-713. Immunohistochemistry for neuronal (NeuN), astrocyte (glial fibrillary acidic protein), and microglial (CD11) specific markers as well as 3H-PK11195 autoradiographic studies were then correlated with the imaging data. Results: Seven days after a unilateral injection of AMPA in the striatum, 11C-DPA-713 exhibits a better contrast between healthy and damaged brain parenchyma than 11C-PK11195 (2.5-fold ± 0.14 increase vs. 1.6-fold ± 0.05 increase, respectively). 11C-DPA-713 and 11C-PK11195 exhibit similar brain uptake in the ipsilateral side, whereas, in the contralateral side, 11C-DPA-713 uptake was significantly lower than 11C-PK11195. Modeling of the data using the simplified reference tissue model shows that the binding potential was significantly higher for 11C-DPA-713 than for 11C-PK11195. Conclusion: 11C-DPA-713 displays a higher signal-to-noise ratio than 11C-PK11195 because of a lower level of unspecific binding that is likely related to the lower lipophilicity of 11C-DPA-713. Although further studies in humans are required, 11C-DPA-713 represents a suitable alternative to 11C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress.