Development of resonant-type microwave reactor and its application to PET radiochemistry

Objectives Microwave (MW) technology has been successfully applied to enhance radiolabeling reactions. When MW is used as a source of energy, the reactions proceed in a shorter time and at higher yields than those performed under the conventional thermal conditions. However, MW reactor is still lacking for widespread use in PET radiochemistry due to its difficulty of controlling MW irradiation under a low amount of reagent. To solve this difficulty, we have developed a novel resonant-type MW reactor oscillated by solid state device. Using the developed MW reactor, we tested if the reactor can focus MW power to a low amount of reagent (solvent: 0.1mL-1.0mL) more effectively compared with magnetron type reactor. In this research, we present the one-pot synthesis of N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) by using the developed MW reactor.

Methods The preparation of [¹⁸F]SFB: (i) [¹⁸F]fuorination of ethyl 4-(trimethylammonium triflate) benzoate at 90°C in MeCN (0.1 mL), (ii) hydrolysis of [¹⁸F]ethyl fluorobezoate with TPAH at 120°C, and (iii) activation of the 4-[¹⁸F]fluorobenzoic acid with TSTU at 90°C. All these reactions were carried out using the developed MW reactor.

Results The developed MW reactor is composed of MW oscillating/controlling unit and MW irradiation unit. MW is oscillated and amplified by solid devices commonly used among cell phone applications. MW irradiation to reagent in borosilicate glass vial is made keeping at frequency at resonance in cylindrical cavity having TM010 mode. Temperature and electric field are continuously optimized by high speed automated feedback control system. The developed MW reactor was substantially superior in terms of thermal capability to commercially available MW reactors. Using the developed MW reactor, [¹⁸F]SFB can be prepared in 25 min including purification process, and the total radiochemical yield was 63±4%.

Conclusions In this study, we have proven that the developed MW reactor can solve the difficulty which conventional magnetron based MW reactors have, readily applicable to the PET radiochemistry.