Radiation dosimetry of androgen receptor (AR) ligand 7α-fluoro-17α-methyl 5α-dihydrotestosterone (FMDHT), a PET probe to detect prostate cancer

Objectives FMDHT is designed as a PET imaging probe to diagnose prostate cancer in patients by targeting AR. With the anticipation of its use in humans, we performed whole body distribution studies in non-human primates (NHP) and calculated an estimated human radiation absorbed dose.

Methods 5 whole-body dynamic PET scans were performed in NHP after injecting 20 ± 13 MBq/kg (0.5 ± 0.3 mCi/kg) of F-18 FMDHT. Scanning was performed under isoflurane anesthesia and continued over 150 min, providing 22 dynamic frames. Additionally, to assess the affect of anesthesia on F-18 accumulation in the liver and gall bladder, an additional PET imaging studies was performed. The NHP was injected with F-18 FMDHT without anesthesia, and at 90 min after injection, animal was anesthetized and scanned over one hour.

Results The F-18 FMDHT showed favorable kinetics and no adverse effects were observed. Initial accumulation of tracer in various tissues was consistent with blood perfusion and rapidly cleared with the time via the hepatobilliary excretion, as anticipated for a steroid based probe. While a high accumulation was observed in gall bladder, this accumulation was strongly dependent on anesthesia (three times higher in anesthetized animal). Since no anesthesia is necessary during human studies, the gall bladder accumulation is anticipated to be much lower. No F-18 accumulation was seen in urinary bladder by 20 min. At 100 min, 2 ± 0.4 %ID was in urinary bladder, suggesting favorable tissue distribution properties which would aid in better visualization of prostate cancer. The estimates of the Effective Dose Equivalent for in human studies was 0.08 mSv/MBq (0.3 rem/mCi).

Conclusions These results suggest that distribution characteristics and kinetics of F-18 FMDHT are favorable to image prostate cancer in humans. Also, injecting 150 - 190 MBq (4 - 5 mCi) of F-18 FMDHT to research volunteer would be within the FDA guidelines.

Research Support NIH RO1 CA10538