Exploratory Evaluation of 18F-FMAU PET in Tracking Response to Docetaxel Treatment in Prostate Tumor-Bearing Mice

Abstract Background The aim of this exploratory preclinical study was to evaluate the efficacy of 18F-FMAU PET in quantitatively measuring response to a chemotherapeutic agent in experimental prostate cancer models. Methods and Materials: Docetaxel (DTX) ‒ a standard therapy agent in castrate-resistant metastatic prostate cancer was used as the chemotherapy drug. Athymic male nu/nu mice were inoculated with PC-3 cells in the right flank. After the tumor diameter reached 5 mm, DTX (24 mg/kg) was injected intravenously twice/week, whereas the control group was intravenously administered with saline. During the therapeutic period, the tumor size and body weight were monitored, and longitudinal PET scans were acquired with 18F-FMAU to evaluate tumor cell proliferation. 18F-FMAU PET scans were performed at 2 h post-injection of 18F-FMAU on days 0, 11, 18, and 22. Biodistribution studies were carried out after the PET scan on day 22. Results Consecutive administrations of DTX were effective in inhibiting PC-3 tumor growth compared to the control group. For PET imaging, PC-3 tumor uptake of 18F-FMAU in the treatment group was increased significantly from 3.09 ± 0.60%ID/g (day 0) to 5.32 ± 0.37%ID/g (day 22), whereas the 18F-FMAU tumor update in the control group remained relatively similar on day 0 (2.37 ± 0.51%ID/g) vs. day 22 (1.83 ± 0.22%ID/g). The tumor-to-muscle uptake ratio of 18F-FMAU was increased from 2.63 ± 0.20 (day 0) to 5.91 ± 1.1 (day 22) in the treatment group. On day 22, no statistical significance was observed on the tumor-to-muscle uptake ratio of 18F-FMAU in the treatment group vs. the control group. The tumor-to-liver uptake ratio of 18F-FMAU was also similar on day 22 in the treatment group (4.29 ± 0.09) vs. the control group (3.83 ± 0.59). Conclusion 18F-FMAU uptake in implanted PC-3 tumors increases with DTX treatment despite the decline in tumor size. Further investigation is needed to decipher the underlying biological mechanism of this flare effect and its relation to the predictability of therapy response.