The aim of this study was to investigate whether 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) can monitor the early response of tumor cell proliferation to charged particle irradiation in vitro and in vivo.
Methods: In vitro, after 0.1, 0.5, 1, 5, and 10 Gy of proton or carbon ion irradiation, (18)F-FLT cell uptake was examined at 24 h and cell proliferation ability was measured from days 1 to 4. In vivo, after 0.5, 1, and 5 Gy of proton or carbon ion irradiation, (18)F-FLT PET imaging was performed on tumor-bearing BALB/c nu/nu mice at 24 h and tumor growth was measured from days 1 to 7. Tumor-to-background ratios of standardized uptake values were calculated to assess the (18)F-FLT accumulation in tumors. Both cells and mice also received x-irradiation as a control.
Results: In vitro, (18)F-FLT cell uptake was significantly lower after 1 Gy of proton irradiation (P < 0.05) and carbon ion irradiation (P < 0.05) and after 5 Gy of x-irradiation (P < 0.01), but cell proliferation ability at these doses did not show significant differences until day 3. In vivo, (18)F-FLT tumor uptake was significantly lower after 1 Gy of proton (P < 0.001) and carbon ion irradiation (P < 0.01) and after 5 Gy of x-irradiation (P < 0.001), but tumor growth did not significantly differ at these doses until day 4 after proton irradiation, day 3 after carbon ion irradiation, and day 5 after x-irradiation.
Conclusion: The reduction in (18)F-FLT uptake after charged particle irradiation was more rapid than the change in tumor growth in vivo or the change in cell proliferation ability in vitro. Therefore, (18)F-FLT is a promising tracer for monitoring the early response of cancer to charged particle irradiation.
Keywords: 3′-deoxy-3′-18F-fluorothymidine (18F-FLT); cell proliferation ability; charged particle irradiation; positron emission tomography (PET); tumor volume.
© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.