HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boutin, H. Articles by Kassiou, M. Search for Related Content PubMed PubMed Citation Articles by Boutin, H. Articles by Kassiou, M.

¹¹C-DPA-713: A Novel Peripheral Benzodiazepine Receptor PET Ligand for In Vivo Imaging of Neuroinflammation

¹ CEA, Institut d'Imagerie Biomédicale, Service hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France; ² INSERM, U803, Orsay, France; ³ Faculty of Life Sciences, Neurobiology Group, University of Manchester, Manchester, United Kingdom; ⁴ CNRS URA 2210, CEA, DSV, 12BM, SHFJ, Orsay, France; ⁵ RRI, ANSTO, Menai, Australia; ⁶ Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia; ⁷ School of Medical Radiation Sciences, University of Sydney, Sydney, New South Wales, Australia; ⁸ School of Chemistry, University of Sydney, Sydney, New South Wales, Australia; and ⁹ Ramaciotti Centre for Brain Imaging, Brain and Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia

Correspondence: For correspondence or reprints contact: Bertrand Tavitian, MD, Laboratoire d'Imagerie Moléculaire Expérimentale, 4 place du général Leclerc, F-91400 Orsay, France.E-mail: bertrand.tavitian{at}cea.fr

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 -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.

Key Words: PET • inflammation • gliosis • peripheral benzodiazepine receptor • PK11195

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

This article has been cited by other articles:

				M. L. James, R. R. Fulton, J. Vercoullie, D. J. Henderson, L. Garreau, S. Chalon, F. Dolle, S. Selleri, D. Guilloteau, and M. Kassiou DPA-714, a New Translocator Protein-Specific Ligand: Synthesis, Radiofluorination, and Pharmacologic Characterization J. Nucl. Med., May 1, 2008; 49(5): 814 - 822. [Abstract] [Full Text] [PDF]

				M.-R. Zhang, K. Kumata, J. Maeda, K. Yanamoto, A. Hatori, M. Okada, M. Higuchi, S. Obayashi, T. Suhara, and K. Suzuki 11C-AC-5216: A Novel PET Ligand for Peripheral Benzodiazepine Receptors in the Primate Brain J. Nucl. Med., November 1, 2007; 48(11): 1853 - 1861. [Abstract] [Full Text] [PDF]