Abstract
BACKGROUND: GBM is associated with poor overall survival partly due to lack of effective treatment. Recently we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and that AR antagonists induced dose-dependent death in several glioblastoma cell lines. Treatment of mice implanted with human GBM with AR antagonists significantly reduced the growth of the tumor and prolonged the lifespan of the mice. 18f-fluorine-radiolabeled Dihidrotestosteron (DHT), a natural ligand of AR, [16β-18F-fluoro-5α-dihydrotestosterone ([(18)F]-FDHT)] is one of the PET tracers used to detect AR expression in metastatic prostate cancer. The aim of this study was to identify AR-expressing GBM tumors in real time using PET-CT scan with [(18)F]-FDHT. MATERIALS AND METHODS: Twelve patients with GBM underwent a dynamic (first 30 min) and whole body static (later 60-80 min) [(18)F]-FDHT PET/CT (296-370 MBq) scans 2-4 days prior to the surgery or biopsy. Protein was extracted from the tumor and subjected to western blot analysis. AR Protein fold change of each tumor sample was calculated by densitometry analysis compared with that of normal brain, following normalization to GAPDH. RESULTS: At ~60 min after injection, 6 of the 12 patients showed significantly higher tumor accumulation of [(18)F]-FDHT, compared to reference tissue (SUV/Control)(mean): 1.33-2.63 fold, (SUV/control)(max): 1.4-3.43 fold. The patient who had higher tumor accumulation of [(18)F]-FDHT, demonstrated also high (1.6-2.27 fold/normal brain) AR protein expression within the tumor. Pearson-correlation-coefficient analysis for the (SUV/Control)(mean) at ~60 min after the injection versus AR protein expression, was positive and significant (R=0.841;p=0.0024). CONCLUSION: This study demonstrated for the first time that [(18)F]-FDHT PET can identify AR-positive-GBM-tumors (with sensitivity and specificity at 100%) and may therefore be a powerful tool to select patients eligible for treatment with AR antagonists. It could possibly be employed also to monitor treatment response and/or progression during the course of therapy.