Monitoring the early biologic response of esophageal carcinoma after irradiation with 18F-FLT: an in-vitro and in-vivo study.

Abstract

The aim of our study was to explore the value of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) and F-FLT PET in monitoring the early biologic response of esophageal carcinoma after irradiation in vitro and in vivo. After 2, 4, and 8 h of irradiation at different doses (0, 5, 10, and 15 Gy) of esophageal carcinoma cells in vitro, the uptake ratio of F-FLT, the relative cell survival rate, and ATP levels were measured. The tumor uptake ratio of F-FLT [tumor-to-nontumor (T/NT)] was measured through PET scans before and on the first, seventh, and 15th day after irradiation. The expression of proliferating cell nuclear antigen and Ki-67 was determined in both untreated and treated tumors. Compared with the control group, the uptake ratio changes of F-FLT after 2 h of irradiation with 5 Gy showed no statistical significance (3.65±0.17 vs. 4.00±0.17%, P>0.05), whereas the uptake ratios of the other groups decreased notably (F=33.93, P<0.01). The differences in the relative survival rates were not statistically significant (F=4.02, P>0.05). Linear regression analysis indicated a significant correlation between F-FLT and ATP levels (r=0.89, P<0.01). On F-FLT PET scan images of the xenografts, the baseline uptake ratio (T/NT) was 2.24±0.06. It decreased to 1.99±0.09, 1.85±0.04, and 1.15±0.10 at 1, 7, and 15 days after irradiation with 10 Gy. Tumor uptake of F-FLT was closely correlated with proliferating cell nuclear antigen and Ki-67 expressions (r=0.83, P<0.001, and r=0.88, P<0.001). The uptake changes of F-FLT in esophageal carcinoma cells and tumor xenografts may reflect the early biological response of esophageal carcinoma after irradiation. Thus, F-FLT PET may be potentially used to monitor the early response of esophageal carcinoma after radiotherapy.