Automated synthesis of 16β-[18F]fluoro-5α-dihydrotestosterone using the FlexLab radiosynthesizer

1010 Objectives 18F labeled 16β-[18F]fluoro-5α-dihydrotestosterone (18F-FDHT) analog is a promising PET tracer for imaging androgen receptors. In this study, we implement and evaluate the automated synthesis of 18F-FDHT using a commercially available synthesizer in order to increase radiolabelling yields, shorten the synthesis time and reduce the radiation exposure to the operator. Methods We choose the FlexLab radiosynthesizer (IPHASE Technologies), which has been proven reliable for complex multi-step radiolabeling. To the dried K[18F]F/kryptofix mixture in reactor 1, was added a solution of triflate precursor (4 mg in 0.5 mL of acetonitrile) and heated to 40 °C for 15 min. Then 10 mL of water was added and the solution transferred to a SPE to trap the radiolabelled intermediates. After rinsing with water, the radiolabelled intermediates were transferred using 1.2 mL of ethanol to reactor 2, which contained 5 mg of NaBH4. Reduction was performed at 20 °C for 7 min, followed by hydrolysis with 1.5 mL of 1M HCl at 80 °C for 7 min. After hydrolysis, 1 mL of 1M NaOH plus 2 mL of water were added and the reaction mixture purified by HPLC. Results Using KHCO3 instead of K2CO3 as base resulted in higher yields and fewer side-products. A gradient elution technique was used to separate 18F-FDHT from radiolabelled by-products. The radioactive peak at 22 min was collected and reformulated using the SePak technique. 18F-FDHT was produced in decay corrected radiochemical yields of 18-23% and a radiochemical purity >98%. The specific activity was >55.5 GBq/µmol (1.5 Ci/µmol), with QC detection limits of 10µg/mL at 210 nm. Conclusions The radiochemical yields of 18F-FDHT using the FlexLab synthesizer was highly reliable (18-23%), producing in 90 min sufficient quantities of the tracer for multiple doses ready for human injections. This method is now validated at our site and will be used to routinely produce 18F-FDHT for clinical trials.