Partners and International Organizations
(English)
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A, B, CZ, DK, FIN, F, D, GR, H, I, NL, N, PL, P, SI, E, S, CH, GB
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Abstract
(English)
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The potential of two new antagonists, 11C-2-[(3-methoxyphenyl)ethynyl]-6-methylpyridine ([11C]-M-MPEP) and its fluoroethyl derivative [18F]-FE-MPEP, as in vivo imaging agents for the metabotropic glutamate receptor subtype 5 (mGluR5) was evaluated. The radiolabeling of M-MPEP with carbon-11 was accomplished by the O-methylation of the desmethyl precursor using carbon-11 methyl iodide. Radiochemical yield ranged from 10-20% and specific activity was 30-60GBq/µmol. The fluorine-18 labeling of FE-MPEP was accomplished in a two-step reaction sequence. Specific radioactivities were above 100GBq/µmol and the radiochemical yield ranged from 10-15%. [11C]-M-MPEP and [18F]-FE-MPEP displayed log D values of 1.3±0.1 and 1.9±0.2, respectively. Despite initial promising results in ex vivo assays using [3H]-M-MPEP, the in vivo investigations employing classical biodistribution and PET studies revealed a lack of specific binding. An unexpected increase in the uptake of both radioligands in rat brain was observed in the presence of M-MPEP as a blocking agent. For both compounds, no radioactive metabolites were detected in the brain, whereas in blood and urine only hydrophilic radioactive metabolites were found. The increased uptake might be due to profound changes in plasma protein binding or enzymatic breakdown under blockade conditions. Both [11C]-M-MPEP and [18F]-FE-MPEP, due to their high non-specific binding are therefore not good candidates for the in vivo imaging of the mGluR5. Further studies using more potent antagonists are needed.
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