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C. Thominiaux,
A. Damont,
B. Kuhnast,
S. Demphel,
S. Le Helleix,
S. Boisnard,
L. Rivron, F. Chauveau,
H. Boutin,
N. Van Camp,
R. Boisgard,
S. Roy,
J. Allen,
T. Rooney,
J. Benavides,
P. Hantraye,
B. Tavitian,
F. Dolle
J Labelled Comp Radiopharm. 01/2010; 53.
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ABSTRACT: In vitro selection of 2'-fluoropyrimidine oligonucleotide aptamers was performed against the N-terminal two-domain fragment of mouse VCAM-1. The SELEX procedure enriched the starting pool in a family of homologous sequences. High binding affinity (10nM) of one member of this family, aptamer 12.11, was demonstrated in a filter binding assay
Bioorg.Med.Chem.Lett. 09/2007; 17.
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ABSTRACT: 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), a PET scan was performed using (11)C-PK11195 or (11)C-DPA-713. Immunohistochemistry for neuronal (NeuN), astrocyte (glial fibrillary acidic protein), and microglial (CD11) specific markers as well as (3)H-PK11195 autoradiographic studies were then correlated with the imaging data. RESULTS: Seven days after a unilateral injection of AMPA in the striatum, (11)C-DPA-713 exhibits a better contrast between healthy and damaged brain parenchyma than (11)C-PK11195 (2.5-fold +/- 0.14 increase vs. 1.6-fold +/- 0.05 increase, respectively). (11)C-DPA-713 and (11)C-PK11195 exhibit similar brain uptake in the ipsilateral side, whereas, in the contralateral side, (11)C-DPA-713 uptake was significantly lower than (11)C-PK11195. Modeling of the data using the simplified reference tissue model shows that the binding potential was significantly higher for (11)C-DPA-713 than for (11)C-PK11195. CONCLUSION: (11)C-DPA-713 displays a higher signal-to-noise ratio than (11)C-PK11195 because of a lower level of unspecific binding that is likely related to the lower lipophilicity of (11)C-DPA-713. Although further studies in humans are required, (11)C-DPA-713 represents a suitable alternative to (11)C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress
J Nucl.Med. 04/2007; 48.
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H. Boutin, F. Chauveau,
C. Thominiaux,
B. Kuhnast,
M.C. Gregoire,
S. Jan,
V. Brulon,
Y. Fontyn,
R. Trebossen,
F. Dolle,
B. Tavitian,
A. Katsifis
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ABSTRACT: Peripheral Benzodiazepine Receptor (PBR) are expressed by microglial cells in several neuropathology. PK11195 is the reference compounds for PBR, and is used for PET imaging but has poor quantification properties. Therefore, investigating new PBR ligand with better
Glia. 01/2007; 55.
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C. Thominiaux,
F. Mattner,
I Greguric,
H. Boutin, F. Chauveau,
B. Kuhnast,
M.-C. Grégoire,
C. Loc’h,
H. Valette,
M. Bottlaender,
Ph. Hantraye,
B. Tavitian,
A. Katsifis,
F. Dollé
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ABSTRACT: C. Thominiaux, F. Mattner, I Greguric, H. Boutin, F. Chauveau, B. Kuhnast, M.-C. Grégoire, C. Loc’h, H. Valette, M. Bottlaender, Ph. Hantraye, B. Tavitian, A. Katsifis and F
Journal Labelled Compounds Radiopharm. 01/2007; 50:229-236.
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ABSTRACT: Aptamers are short oligonucleotides selected from large combinatorial pools of sequences for their capacity to bind to many different targets ranging from small molecules (amino acids, antibiotics...) to proteins or nucleic acid structures. Aptamers present the same high specificity and affinity for their targets as antibodies. In addition to efficient binding, aptamers have been shown in many cases to display an inhibitory activity against their targets. Many aptamers are now being developed against biomedical relevant targets, and one aptamer that inhibits the human VEGF165 already received approval for the treatment of age-related macular degeneration. Here we discuss the principles and the practical way of selecting aptamers (SELEX technology) as well as the structural basis for their performance as ligands. A wide scope of applications is described - aptamers have been used as tools for studying nucleic acids/proteins interactions, detecting, purifying or imaging target molecules, regulating gene expression - and includes recent developments of aptamers for therapy and diagnosis.
Pathologie Biologie 06/2006; 54(4):251-8. · 1.53 Impact Factor
