Development of a resonant‐type microwave reactor and its application to the synthesis of positron emission tomography radiopharmaceuticals

Abstract

Microwave technology has been successfully applied to enhance the effectiveness of radiolabeling reactions. The use of a microwave as a source of heat energy can allow chemical reactions to proceed over much shorter reaction times and in higher yields than they would do under conventional thermal conditions. A microwave reactor developed by Resonance Instrument Inc. (Model 520/521) and CEM (PETWave) has been used exclusively for the synthesis of radiolabeled agents for positron emission tomography by numerous groups throughout the world. In this study, we have developed a novel resonant-type microwave reactor powered by a solid-state device and confirmed that this system can focus microwave power on a small amount of reaction solution. Furthermore, we have demonstrated the rapid and facile radiosynthesis of 16α-[(18)F]fluoroestradiol, 4-[(18)F]fluoro-N-[2-(1-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinylbenzamide, and N-succinimidyl 4-[(18)F]fluorobenzoate using our newly developed microwave reactor.

Radiosynthesis of novel pitavastatin derivative ([18F]PTV‐F1) as a tracer for hepatic OATP using a one‐pot synthetic procedure

“…As Scheme shows, the [ 18 F]PTV‐F1 compound was synthesized in 3 steps involving aliphatic radiofluorination in the presence of Kryptofix2.2.2, deprotection under acidic conditions, and alkaline hydrolysis of the lactone compound. In the first step, the nucleophilic substitution of PTV‐F1 precursor 2 was accomplished with 18 F‐fluoride in the presence of Kryptofix2.2.2 and potassium carbonate in acetonitrile at 120°C for 1 minute under microwave irradiation using the resonant‐type microwave reactor . The [ 18 F]fluorination was accomplished with a high radiochemical yield (>95%, calculated by radio–thin‐layer chromatography [TLC]).…”

“…In the first step, the nucleophilic substitution of PTV-F1 precursor 2 was accomplished with 18 F-fluoride in the presence of Kryptofix2.2.2 and potassium carbonate in acetonitrile at 120°C for 1 minute under microwave irradiation using the resonant-type microwave reactor. 17 The [ 18 F]fluorination was accomplished with a high radiochemical yield (>95%, calculated by radio-thin-layer chromatography [TLC]). The deprotection of the acetonide and tert-butyl ester groups was conducted using hydrochloric acid at 100°C for 1 minute under microwave irradiation to give [ 18 was purified by HPLC.…”

<i>In Vivo</i> Molecular Imaging

“…Thus we designed and developed an effective synthetic method for probes labeled with short half-life radioisotopes. [104][105][106] For clinical use of these molecular imaging probes, we designed and developed a computer-controlled automatic synthesizer. 107) …”

Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip

“…The radioactivity of 18 F was measured using a curiemeter (IGC-3, Aloka) or NaI (Tl) gamma scintillation counter (Cobra Auto-Gamma Counter 5003, Perkin-Elmer (Packard), Waltham, MA, USA). A screw-cap pressure vessel was used as a batch reactor (purchased from Oofuna, Ltd., Osaka, Japan) [37]. Most chemicals were reagent-grade, purchased from Merck (Darmstadt, Germany) and Sigma-Aldrich (St. Louis, MO, USA), and used without further purification.…”