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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REFERENCES
- Imaging of cell proliferation: status and prospects.J Nucl Med. 2008; 49: 64S-80S
- PET imaging of cellular proliferation.Radiol Clin North Am. 2005; 43: 153-167
- PET radiotracers for imaging the proliferative status of solid tumors.PET Clin. 2009; 4: 1-15
- Imaging cellular proliferation as a measure of response to therapy.J Clin Pharmacol. 2001; : 96S-103S
- Human thymidine kinase I. Regulation in normal and malignant cells.Adv Enzym Regul. 1995; 35: 69-89
- An assessment of early response to targeted therapy via molecular imaging: a pilot study of 3′-deoxy-3′[18F]-fluorothymidine positron emission tomography 18F-FLT PET/CT in prostate adenocarcinoma.Diagnostics. 2017; 7: 20
- Radiolabeled 2′-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2′-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice.Cancer Chemother Pharmacol. 2002; 49: 419-424
- Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine an thymidine analogs.J Nucl Med. 2003; 44: 2027-2032
- Tracking cellular stress with labeled FMAU reflects changes in mitochondrial TK2.Eur J Nucl Med Mol Imaging. 2008; 35: 1480-1488
- Synthesis of 2′-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET.Nucl Med Biol. 1995; 22: 783-789
- Imaging DNA synthesis in vivo with 18F-FMAU and PET.J Nucl Med. 2005; 46: 292-296
- Synthesis of 2’-deoxy-2’-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation: synthesis of [18F]labeled FAU, FMAU, FBAU, FIAU.Nucl Med Biol. 2003; 30: 215-224
- Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([18F]-FMAU).Nucl Med Biol. 2012; 39: 1019-1025
- Exploring solvent effects in the radiosynthesis of 18F-labeled thymidine analogues toward clinical translation for positron emission tomography imaging.ACS Pharmacol Transl Sci. 2021; 4: 266-275
- New treatments for men with castration-resistant prostate cancer: can we move from small steps to giant leaps?.Eur Urol. 2014; 65: 300-302
- What medical, urologic, and radiation oncologists want from molecular imaging of prostate cancer.J Nucl Med. 2016; 57: 6S-12S
- Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer.Eur J Nucl Med Mol Imaging. 2021; 48: 469-476
- Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT.Cancer Imaging. 2016; 16: 34
- Characterizing tumors using metabolic imaging: PET imaging of cellular proliferation and steroid receptors.Neoplasia. 2000; 2: 71-88
- Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells.Oncogene. 2004; 23: 7018-7030
- Proliferation markers for the differential diagnosis of tumor and inflammation.Curr Pharm Dis. 2008; 14: 3326-3339
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.
