Predictive value of early stage uptake of 3'-deoxy-3'-¹⁸F-fluorothymidine in colorectal cancer treated with charged particle irradiation.

Objectives The objective of this study was to investigate whether 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) could monitor early responses of malignant tumors to charged particle irradiation.

Methods In cell experiments, colorectal cancer cell line Colon26 cells were used. ¹⁸F-FLT cell uptake was examined at 24 h after irradiation with 0.1 Gy, 0.5 Gy, 1 Gy, 5 Gy and 10 Gy of proton irradiation and carbon ion irradiation, while cell viability was measured from day 1 to day 4 after irradiation. In animal experiments, ¹⁸F-FLT positron emission tomography (PET) imaging was performed on Colon26-bearing BALB/c nu/nu mice at 24 h after irradiation with 0.5 Gy, 1 Gy, and 5 Gy of proton or carbon ion irradiation, and tumor growth from day 1 to day 7 after irradiation was measured. Tumor-to-background ratios of SUV were calculated to assess the ¹⁸F-FLT accumulation in tumors. Both cells and mice were also irradiated with X-ray irradiation as a control.

Results In cell experiments, ¹⁸F-FLT cell uptake was significantly lower at 1 Gy after proton (P < 0.05) and carbon ion irradiation (P < 0.05), and at 5 Gy after X-ray irradiation (P < 0.01), while cell viability at the above doses did not show significant differences until day 3. In animal experiments, ¹⁸F-FLT tumor uptake was significantly lower for 1 Gy after proton (P < 0.001) and carbon ion irradiation (P < 0.01), and for 5 Gy after X-ray irradiation (P < 0.001), while the tumor growth did not show significant differences at the above doses until day 4 after proton, day 3 carbon ion, and day 5 X-ray irradiation.

Conclusions The reduction of ¹⁸F-FLT uptake after charged particle irradiation was more rapid than the change of tumor growth in vivo and the change of cell viability in vitro. Therefore, ¹⁸F-FLT is a promising tracer for monitoring early responses of cancer to charged particle irradiation.

Research Support This study was partially supported by a research fund of the Wakasa Wan Energy Research Center and JSPS KAKENHI Grant Number 24249065.