Development of microwave-based automated nucleophilic [18F]fluorination system and its application to the production of [18F]flumazenil

Mandap, Katheryn S.; Ido, Tatsuo; Kiyono, Yasushi; Kobayashi, Masato; Lohith, Talakad G.; Mori, Tetsuya; Kasamatsu, Shingo; Kudo, Takashi; Okazawa, Hidehiko; Fujibayashi, Yasuhisa

doi:10.1016/j.nucmedbio.2009.01.011

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 403-409, May 2009

Development of microwave-based automated nucleophilic [¹⁸F]fluorination system and its application to the production of [¹⁸F]flumazenil

Katheryn S. Mandap
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Tatsuo Ido
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
- Japan Radioisotope Association, Tokyo 113-8491, Japan
Yasushi Kiyono
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
- Corresponding author. Tel.: +81 776 61 8420; fax: +81 776 61 8170.
Masato Kobayashi
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Talakad G. Lohith
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Tetsuya Mori
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Shingo Kasamatsu
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Takashi Kudo
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Hidehiko Okazawa
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Yasuhisa Fujibayashi
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan

Received 24 December 2008; received in revised form 21 January 2009; accepted 23 January 2009. published online 31 March 2009.

Abstract

Introduction

This study presents the development of an automated radiosynthesis system integrating a microwave reactor and its subsequent application in the synthesis of [¹⁸F]flumazenil, a potentially useful compound in the evaluation of central benzodiazepine receptor density.

Methods

Preparation of dry [K/K₂₂₂]⁺¹⁸F⁻ complex and radiofluorination of the nitro-flumazenil precursor were achieved using the developed microwave-based radiosynthesis system. The crude product was prepurified in a C18 cartridge followed by reversed-phase preparative high-performance liquid chromatography. The isolated [¹⁸F]flumazenil was evaporated in vacuo and reconstituted in an ethanol-free solution.

Results

Optimum incorporation of ¹⁸F⁻ in the nitro-precursor was achieved in 5 min time utilizing 2 mg of precursor in N,N-dimethylformamide reacted at 160°C which gave an incorporation yield of 40±5%. The radiochemical yield obtained at the end of synthesis was 26±4% (EOB) with a radiochemical purity of >99% and a total synthesis time of about 55–60 min. The produced [¹⁸F]flumazenil was observed to be stable for at least 8 h.

Conclusion

The developed [¹⁸F]flumazenil radiosynthesis system offers shorter reaction time, simplicity in operation and applicability for use in routine clinical practice.

Keywords: [¹⁸F]flumazenil, Microwave, Radiofluorination, Central benzodiazepine receptors