||Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy
Tomoya , Uehara ,
Mariko, Watanabe ,
Hiroyuki, Suzuki ,
Furusawa, YoshiyaYasushi, Arano,
e0173096-13 , 2017-02 , Public Library of Science
Abstract: L-[methyl-11C]Methionine (11C-Met) is useful for estimating the therapeutic efficiencies of conventional radiotherapy and carbon-ion radiotherapy. Due to the short half-life of 11C, the development of other radionuclide-labeled probes, particularly those that afford similar diagnostic information to 11C-Met, is being sought. Since the energy-dependent cellular functions involved in 11C-Met reflect radiotherapeutic effects, we herein evaluated the activity of energy-dependent amino acid transport system A in order to estimate radiotherapeutic effects using the specific system A substrate, alpha-[1-14C]-methyl-aminoisobutyric acid (14C-MeAIB) because 18F- or 123I-labeled probes for system A have already been produced. Methods: A carbon-ion beam was used as the radiation source. Cellular growth and the accumulation of 14C-MeAIB or L-[14C-methyl]methionine (14C-Met) were evaluated over time in in vitro cultured human salivary gland (HSG) tumor cells (3 Gy) or in vivo murine xenografts of HSG tumors (6 or 25 Gy) before and after irradiation with the carbon-ion beam. Results: In an in vitro study, after 3-Gy irradiation dose, the uptakes of 14C-Met and 14C-MeAIB decreased over a 5-day period. In xenografts of HSG in mice, in vivo tumor re-growth was observed on day 10 after the 6-Gy irradiation dose, but was not detected after the 25-Gy irradiation dose. Consistent with these results, no significant differences were noted in the in vivo tumor uptake of 14C-MeAIB before and after the 6-Gy irradiation dose, whereas a significant decrease was observed after the 25-Gy irradiation dose. Conclusions: The results of the present study indicate that the activity of system A reflects the therapeutic efficacy of carbon-ion radiotherapy as well as 14C-Met. Therefore, 18F- or 123I-labeled probes for system A have potential as widely usable probes to evaluate the effects of tumor radiotherapy.