Fully-automated synthesis of 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Abstract

Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29 ± 5% (n = 7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use.

Fully automated synthesis of [18F]fluoro‐dihydrotestosterone ([18F]FDHT) using the FlexLab module

“…Total synthesis time including radiotracer reformulation was 90 min. Although synthesis time and yields are very similar to the results reported by others, it is important to note that these results were achieved using only 4 mg of [ 18 F]FDHT precursor …”

“…It also uses 50% less [ 18 F]FDHT precursor than other methods. Decay corrected radiochemical yields, specific activity and overall synthesis time are comparable to the method published by Lazari et al . We believe that these modifications can easily be adapted to suit other automated synthesis modules.…”

“…A recently published automated synthesis using the ELIXYS synthesiser uses in‐house made drying cartridges and the rotary evaporation technique for the reformulation of [ 18 F]FDHT …”

18F-labeled anti-human CD20 cys-diabody for same-day immunoPET in a model of aggressive B cell lymphoma in human CD20 transgenic mice

“…Serial imaging using [ 18 F]FDG PET/CT followed the next day by [ 18 F]FB-GAcDb immunoPET/CT was conducted on mice with limited or extensive disease and on mice injected with antigen negative A20 cells as control. [25] were generated using the ELIXYS automated radiosynthesizer (Sofie Biosciences) [33]. Radiochemical purity was confirmed to be >95% by radio-HPLC, and radiochemical identity was confirmed in analytical HPLC by comparison with co-injected standard.…”

Evaluation of Castration-Resistant Prostate Cancer with Androgen Receptor–Axis Imaging

“…About 8 y later, the first in-human PET imaging studies in castrate patients were reported by Memorial Sloan Kettering Cancer Center and Washington University (5-7). The production methodology developed by Washington University continues to be used to this day, though recent improvements have been made in the radiosynthetic chemistry (8) and to the production process by automation (9,10).…”