|
内容記述 |
Introduction: 18F-Fluoroethyl groups are beneficial for the transformation of promising 11C-labeled PET tracers. Therefore, many 18F-fluoroethylated PET tracers have been developed. However, 18F-fluoroethylation via 18F-fluoroethyl reagents and the corresponding desmethyl precursor requires multi-step radiosynthesis and multi reactors. To overcome these limitations, a straightforward one-pot method for 18F-fluoroethylation without azeotropic drying of [18F]F- was developed by Kniess et al [Ref. 1]. Furthermore, we improved this procedure to synthesize [18F]FEDAC as a TSPO imaging tracer, and [18F]FET as a tumor imaging tracer [Ref. 2]. Here, to continuously apply this procedure (the simplified one-pot 18F-fluoroethylation), we synthesized 18F-fluoroethylated analogs of 2-(4,5-dihydro-1H-imidazol-2-yl)-1-methyl-1H-indole (BU99008) as useful PET tracers for imaging the imidazoline I2 receptors. 18F-Fluoroethylated BU99008 ([18F]FEBU) was previously synthesized automatically via muti-steps using an 18F-labelling synthesizer with multi-pots reactors [Ref. 3]. To achieve easy radiosynthesis with short time, we synthesized [18F]FEBU and [18F]FEBU-d4 using the simplified one-pot 18F-fluoroethylation. Methods: [18F]FEBU or [18F]FEBU-d4 was automatically synthesized by the reaction of desmethyl-BU99008 (BU99007) with [18F]fluoroethyl- or [18F]fluoroethyl-d4-tosylate as a radiolabeling agent. Firstly, [18F]fluoroethyl- or [18F]fluoroethyl-d4-tosylate was synthesized in situ by 18F-fluorination within a mixture of 18F- in 30 mmol/L of kryptofix 2.2.2 in acetonitrile (30 µmol/0.98 mL) and 750 mmol/L K2CO3 solution (15 µmol/0.2 mL), bis(tosyloxy)ethane or bis(tosyloxy)ethane-d4 (15 µmol), and cesium carbonate (15 µmol). Next, without purification, a solution of BU99007 (15 µmol) in N,N-dimethylformamide (0.5 mL) and cesium carbonate (15 µmol) was added to this mixture, and the reaction mixture was heated at 110oC for 10 min. The mixture was diluted and transferred to semi-preparative HPLC. The [18F]FEBU or [18F]FEBU-d4 fraction was evaporated for dryness, dissolved in physiological saline including Tween 80, and filtered to obtain the [18F]FEBU or [18F]FEBU-d4 injection.Results: Using the simplified one-pot 18F-fluoroethylation procedure, the radiochemical yields of [18F]FEBU and [18F]FEBU-d4 from 18F- at the end of irradiation (EOI) were 8.4±1.7% (n = 3) and 4.9±1.0% (n = 3), respectively. The radiosynthesis time and radiochemical purity were approximately 70 min after EOI and over 95%, respectively. In the previous study via muti-steps, the radiochemical yield from 18F- at EOI was 10.1± 5.3% (n = 10) [Ref. 3]. Although the simplified one-pot 18F-fluoroethylation procedure needed more precursor (15 µmol) for radiosynthesis, compared to the muti-steps for 5.4 µmol precursor [Ref. 3], the present radiosynthesis time using the one-pot procedure (70 min) was shorter than that using the muti-steps (90 min) [Ref. 3].Conclusion: We have successively synthesized [18F]FEBU and [18F]FEBU-d4 using the simplified one-pot 18F-fluoroethylation, and achieved automation for all radiosynthesis processes using an 18F-labeling synthesizer. |
