Automated Production of GMP-Compliant ~18F-FES as an Estrogen Receptor Ligand for Breast Cancer Imaging

摘要

Background: To assist breast cancer treatment, an accurate method for patient selection and response prediction to endocrine and other targeted therapy is required. 16α-~18F-fluoro-17β-estradiol (~18F-FES) is currently the only ER-targeted positron emission tomography (PET) agent validated with many clinical trials for patients with breast cancer. The aim of this study was to automatically produce ~18F-FES and setup the quality control (QC) tests in conditions that meet good manufacturing practice (GMP) requirements. Methods: With commercial cassette and reagent kit, the syntheses of ~18F-FES were successfully validated under GMP conditions. Results: ~18F-FES has been successfully validated under GMP conditions, resulting in radiochemical yield of 6.9 ± 1.7 % (EOS) within 74 ± 0 min (n = 4) of synthesis time. Radiochemical purity and specific activity of each batch were > 95% and 613 ± 430 GBq/μmol (EOS, n = 4), respectively. The specification and the complete QC results of three consecutive batches of ~18F-FES were also presented. Conclusions: The use of disposable cassette and cartridge purification not only simplifies the operation and shortens the synthesis time, but also is convenient to produce qualified ~18F-FES for clinical and pre-clinical use with common ~18F-FDG module. Now, ~18F-FES is ready to use in various clinical or pre-clinical studies at National Taiwan University Hospital (NTUH).