Facile and rapid one-step radiosynthesis of [18F]BAY94-9172 with a new precursor

Wang, Hongliang; Shi, Huixian; Yu, Haiyan; Jiang, Shende; Tang, Ganghua

doi:10.1016/j.nucmedbio.2010.06.009

« Previous Next »Nuclear Medicine and Biology
Volume 38, Issue 1 , Pages 121-127, January 2011

Facile and rapid one-step radiosynthesis of [¹⁸F]BAY94-9172 with a new precursor

Hongliang Wang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
Huixian Shi
- School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Haiyan Yu
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
Shende Jiang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
- Corresponding authors. Shende Jiang is to be contacted at the School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China, Tel.: +86 22 27892860; fax: +86 22 27892860. Ganghua Tang, Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China, Tel.: +86 20 87755766x8315.
Ganghua Tang
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
- Corresponding authors. Shende Jiang is to be contacted at the School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China, Tel.: +86 22 27892860; fax: +86 22 27892860. Ganghua Tang, Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China, Tel.: +86 20 87755766x8315.

Received 20 January 2010; received in revised form 22 June 2010; accepted 23 June 2010. published online 18 August 2010.

Abstract

Introduction

[¹⁸F]BAY94-9172 (Florbetaben) (Compound 8) is a positron emission tomography (PET) tracer that is currently in Phase III study for in vivo mapping of fibrillar amyloid β as a pathological hallmark for Alzheimer's disease. This work reports new methods for the synthesis of [¹⁹F]BAY94-9172 and its two different precursors and radiosynthesis of [¹⁸F]BAY94-9172 with the two precursors by purification using Sep-Pak cartridge.

Methods

The reference standard [¹⁹F]BAY94-9172 and the new precursor (Compound 9) were obtained from the reactions of (E)-4-methylamino-4′-hydroxystilbene (Compound 1) with methanesulfonic acid 2-[2-(2-fluoro-ethoxy)-ethoxy]-ethyl ester (Compound 11) and methanesulfonic acid 2-[2-(2-methanesulfonyloxy-ethoxy)-ethoxy]-ethyl ester (Compound 13), respectively. The reported precursor (Compound 6) is an N-BOC-protected mesylate compound, which was obtained from Compound 9. The one-step radiosynthesis of [¹⁸F]BAY94-9172 was carried out in the modified PET-MF-2V-IT-1 synthesizer by [¹⁸F]fluorination of the new precursor (Compound 9) and purification with plus C18 Sep-Pak cartridges and was compared with two-step one-pot radiosynthesis using the reported precursor (Compound 6) and Sep-Pak cartridge purification.

Results

For one-step radiosynthesis, the uncorrected radiochemical yield of [¹⁸F]BAY94-9172 was 23±3% (n=5, based on [¹⁸F]fluoride) within 30 min and the radiochemical purity was greater than 95%. For two-step one-pot radiosynthesis, the uncorrected radiochemical yield of [¹⁸F]BAY94-9172 was 17±2% in 45 min (n=4, based on [¹⁸F]fluoride) with the radiochemical purity being above 95% after the Sep-Pak cartridge purification.

Conclusion

[¹⁹F]BAY94-9172 and the two precursors were synthesized by a short synthetic route. Compared with HPLC purification, the use of Sep-Pak purification of [¹⁸F]BAY94-9172 reduced the total radiosynthesis time. The one-step radiosynthesis of [¹⁸F]BAY94-9172 is convenient and can easily be applied to the commercial PET tracer synthesizer for automated synthesis.

Keywords: Alzheimer's disease, PET, BAY94-9172, Florbetaben, Radiosynthesis