Objectives
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.
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 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.
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 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).
Conclusion
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.
Key Words
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Article Info
Publication History
Published online: September 29, 2022
Accepted:
September 5,
2022
Received in revised form:
August 22,
2022
Received:
May 26,
2022
Publication stage
In Press Corrected ProofFootnotes
Funding: Supported in part by grants R21-CA142426 and P30‐CA014089 from the U.S. National Institutes of Health .
Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Identification
Copyright
© 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
