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Updated: May 26, 2026
10:04
Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models
Published on: March 13, 2018
[(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells.
Cathy C Zhang1, Zhengming Yan, Wenlin Li
1Oncology Research Unit, La Jolla Laboratories, Pfizer Global Research and Development, San Diego, California 92121, USA. cathy.zhang@pfizer.com
Summary
[(18)F]FLT-PET imaging shows promise for monitoring cancer therapy. However, tumor thymidine levels can affect its accuracy in measuring cell proliferation. Careful validation is crucial for reliable results in tracer-avid tumors.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Imaging
Background:
- [(18)F]FLT (3'-Fluoro-3' deoxythymidine)-PET imaging is a proposed method for assessing in vivo tumor cell proliferation.
- Validation of [(18)F]FLT-PET for xenograft proliferation measurement and therapy monitoring is essential.
Purpose of the Study:
- To validate [(18)F]FLT-PET imaging for measuring xenograft proliferation.
- To assess its utility in monitoring targeted anticancer therapies.
Main Methods:
- Evaluation of factors influencing [(18)F]FLT-PET imaging outcomes in xenografts, including nucleoside transporters, thymidine kinase 1, and the FLT to thymidine ratio.
- Comparison of [(18)F]FLT tracer avidity with other proliferation markers.
- Assessment of bromdeoxyuridine (BrdUrd) uptake as a proliferation marker.
Main Results:
- [(18)F]FLT and [(3)H]thymidine avidity did not consistently reflect tumor growth rates across xenograft types, despite high Ki67 and TK1 expression.
- Plasma FLT to thymidine ratio was low (approx. 1:200) at preclinical imaging doses, with variable tumor thymidine levels inversely correlating with FLT avidity.
- High-dose BrdUrd (50 mg/kg) showed a strong correlation with tumor proliferation.
- In FLT-avid models, [(18)F]FLT-PET imaging predicted response to the CDK4/6 inhibitor PD-0332991.
Conclusions:
- Tumor thymidine levels are a critical factor influencing the correlation between [(18)F]FLT uptake and cell proliferation.
- [(18)F]FLT-PET imaging can be a valuable tool for monitoring antiproliferative therapies in specific tracer-avid malignancies, provided careful validation is performed.
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