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内容記述 |
Background: [11C]TGN-020 has been developed as a positron emission tomography (PET) tracer for imaging aquaporin-4 (AQP4) in the brain and used in clinical studies. Previously, [11C]TGN-020 was synthesized through the acylation of [11C]nicotinic acid, produced by the reaction of 3-bromopyridine and n-butyllithium with [11C]CO2, with 2-amino-1,3,4-thiadiazole. In this study, to enhance the automated radiosynthesis efciency of [11C]TGN-020, we optimized its radiosynthesis procedure using our inhouse developed 11C-labeling synthesizer.
Results: [11C]TGN-020 was synthesized via direct [11C]CO2 fxation using n-butyllithium and 3-bromopyridine in tetrahydrofuran, followed by treatment of lithium [11C]nicotinic acetate with isobutyl chloroformate and subsequent acylation with 2-amino-1,3,4-thiadiazole in the presence of N,N-diisopropylethylamine. The optimized process signifcantly improved the radiosynthesis efciency of [11C]TGN-020, achieving a high radiochemical yield based on [11C]CO2 (610?1700 MBq, 2.8±0.7%) at the end of synthesis (n=12) and molar activity (Am) of 160?360 GBq/μmol at the end of synthesis (n=5). The radiosynthesis time and radiochemical purity were approximately 60 min
and>95% (n=12), respectively. PET studies based on [11C]TGN-020 with diferent Am values were performed using healthy rats. The radioactive uptake of [11C]TGN-020 with high Am in the cerebral cortex was slightly higher than that with low Am.
Conclusions: [11C]TGN-020 with high Am was obtained in reproducible radiochemical yield. Overall, the proposed optimization process for the radiosynthesis of [11C]TGN-020 can facilitate its application as a PET radiopharmaceutical for clinical use.
Keywords: Carbon-11, Radiosynthesis, [11C]TGN-020, Positron emission tomography, Aquaporin-4 |
