Early prediction of the radiation therapeutic effect against cervical cancer by 3'-deoxy-3'[¹⁸F]fluorothymidine

Objectives: We evaluate the efficiency of particle radiation therapy and the early prediction of the radiation therapeutic effects using 3’-deoxy-3’-[¹⁸F]fluorothymidine ([¹⁸F]FLT) as a PET tracer. In particular, cervical cancer has a high incidence among young people, early prediction of the therapeutic effect is considered to be very important. In this study, squamous cell carcinoma cells, which are generally considered to be highly responsive to radiation therapy, and adenocarcinoma cells, which are ineffective, are selected. Using these cells, and efficiency of particle radiation therapy and whether [¹⁸F]FLT can be used for the early prediction of the therapeutic effect were evaluated in vitro.

Methods: HeLa (Human cervix adenocarcinoma), SiHa (Human cervix squamous cell carcinoma) and ME-180 (Hunan cervix epidermoid carcinoma derived from metastatic site) were used in this study, To the cells cultured, X-ray, proton and carbon ions were irradiated with doses at 0-10 Gy. Time-courses of cell growth were evaluated by cell counting up to 96 h from the irradiation. Also, [¹⁸F]FDG and [¹⁸F]FLT cell uptake study was carried after 26 h from the irradiation.

Results: In all three cells, cell growth was suppressed in dose-dependent manner. The irradiation dose for cell growth 50% inhibition at 96 h from the irradiation was shown in Table 1. High cell growth suppression effect by carbon irradiation could be observed. In addition, the irradiation dose for cell growth 50% inhibition on HeLa cells was higher than the other two cells, considering to be reflected the low efficacy of radiation therapy against adenocarcinoma cells.After 26 h from the irradiation, cell uptake of [¹⁸F]FDG and [¹⁸F]FLT were evaluated. Signification decrease of [¹⁸F]FLT uptake was observed in the groups, which cell proliferation was suppressed at 96 h post-irradiation. Then, the relative cell number at 96 h after the irradiation and relative [¹⁸F]FLT at 26 h were plotted. These two factors showed high linear correlations (Figure 1). Conclusion: In all three types of cells evaluated in this study, the cell uptake of [¹⁸F]FLT at 26 h from the irradiation showed high linear correlation with the cell growth inhibitory effect thereafter. Therefore, [¹⁸F]FLT exhibited excellent properties as a marker for predicting the therapeutic effect in the early stage of the radiation therapy. Acknowledgement: This study was partially supported by a research fund of the Wakasa Wan Energy Research Center

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