Predictive value of early-stage uptake of 39-deoxy-39-18FFluorothymidine in cancer cells treated with charged particle irradiation

Abstract

The aim of this study was to investigate whether 3'-deoxy-3'-18Ffluorothymidine (18F-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, 18F-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, 18F-FLT PET imaging was performed on tumorbearing 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 18F-FLT accumulation in tumors. Both cells and mice also received x-irradiation as a control. Results: In vitro, 18F-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, 18F-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 18F-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, 18F-FLT is a promising tracer for monitoring the early response of cancer to charged particle irradiation.