Murphy and van Dam labs complete the first fully-automated synthesis of 18F-FDHT on the ELIXYS radiosynthesizer

Prostate cancer is the second leading cause of cancer-related deaths in men, and methods of early detection and monitoring are necessary for management of the disease. In recent work published in the journal Applied Radiation and Isotopes, the Murphy and van Dam labs contribute to this goal by describing the automated production of a positron emission tomography (PET) diagnostic probe for prostate cancer, 18F-FDHT.


PET is a noninvasive imaging modality which uses radiolabeled probes to detect specific biomarkers - characteristics that can be measured as readouts of biological states. One biomarker for some types of prostate cancer is an increased expression of the androgen receptor (AR), a protein on the surface of cells that can interact with certain hormones.  Labeling an AR ligand, such as dihydrotestosterone (DHT), with radioactivity, followed by injection into a patient and subsequent PET imaging, enables researchers to identify suspected tumors via high AR expression compared to the surrounding tissue.


Clinical studies with 18F-FDHT (the fluorine-18 radiolabeled version of DHT, for PET imaging) have shown that it has high potential as a diagnostic tool. Currently, there are limited sites in the country where 18F-FDHT can be used as it requires manual synthesis by trained radiochemists. If 18F-FDHT is to be broadly utilized as a clinical diagnostic agent, it must be produced reliably and routinely at multiple locations. In this study from the Murphy and van Dam labs, Lazari et al. demonstrate the first fully-automated synthesis of 18F-FDHT on the ELIXYS radiosynthesizer for production of several patient doses. Translation of the manual 18F-FDHT synthesis protocol into an automated one enables facilities with the ELIXYS radiosynthesizer to practically and routinely produce 18F-FDHT for diagnostic molecular imaging in prostate cancers.


Citation: Fully-automated synthesis of 16ß-18F-Fluoro-5alpha-dihydrotestosterone (18F-FDHT) on the ELIXYS radiosynthesizer, Lazari, M.; Lyashchenko, S. K.; Burnazi, E. M.; Lewis, J. S.; van Dam, R. M.; Murphy, J. M. Appl. Radiat. Isot. 2015, 103, 9 - 14. DOI:10.1016/j.apradiso.2015.05.010



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.


Summary by Amanda Freise