Tracking Docetaxel-Induced Cellular Proliferation Changes in Prostate Tumor-Bearing Mice with ¹⁸F-FMAU PET

The aim of this exploratory preclinical study was to evaluate the efficacy of ¹⁸F-FMAU PET in quantitatively measuring cellular proliferation changes in response to a chemotherapeutic agent in experimental prostate cancer models.

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 a week, whereas the control group was intravenously administered with saline. The tumor size and body weight were monitored, and longitudinal PET scans were acquired with ¹⁸F-FMAU to evaluate tumor cellular proliferation. ¹⁸F-FMAU PET scans were performed at 2 hours post-injection of ¹⁸F-FMAU on days 0, 11, 18, and 22. Biodistribution studies were carried out after the PET scan on day 22.

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 DTX 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 stable 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 DTX group. On day 22, no statistical significance was observed in the tumor-to-muscle uptake ratio of ¹⁸F-FMAU in the DTX group vs. the control group. The tumor-to-liver uptake ratio of ¹⁸F-FMAU was also similar on day 22 in the DTX group (4.29 ± 0.09) vs. the control group (3.83 ± 0.59).

¹⁸F-FMAU uptake in implanted PC-3 tumors increases with DTX despite inhibiting tumor growth. Further investigation is needed to decipher the underlying biological mechanism of this apparent flare effect and its relation to the predictability of tumor response to DTX.