Microwave-assisted rapid synthesis of [¹⁸F]fluoroestradiol for medical use

Objectives It has been proven that microwave heating (MW) not only increases the product yield of a chemical reaction but also shortens the reaction time, increases reproducibility, and produces cleaner product mixture when compared with conventional heating (CH). Realizing these advantages, microwave reactors are introduced in radiopharmaceutical development as an alternative to CH. [¹⁸F]fluoroestradiol is a clinically important PET tracer in nuclear medicine for investigating primary and metastatic breast cancer. To improve its radiochemical yield and purity for efficient medical use, a significant amount of work was conducted on [¹⁸F] FES synthesis using CH, but no considerable effort has been made to use MW technique.

Methods The impact of microwave (MW) heating on both fluorination and hydrolysis reactions was scrutinized. Chemical and radiochemical purity and radiochemical yields were investigated for CH and compared with MW-assisted radiosyntheses. Quality control (QC) tests of [¹⁸F] FES produced by MW were performed following validated analytical methods filed in IND #79,005 [1]. Microwave-assisted clinical preparation of [¹⁸F]FES will be presented in great detail.

Results Microwave assisted synthesis is quicker and side products are notably fewer. The overall isolated radiochemical yield of purified [¹⁸F]FES was ~ 55% with MW vs ~30% with CH (~ 85% improvement). QC test results demonstrated that [¹⁸F] FES produced by microwaving was suitable for human administration.

Conclusions Microwaving should be a preferred heating technique for producing [¹⁸F] FES.

Research Support Funded by NCI/NIH, Contract No. HHSN261200800001E