The effects of pulsed radiotherapy on tumor oxygenation in two murine models of head and neck squamous cell carcinoma
Menée à l'aide d'une xénogreffe de carcinome épidermoïde de la tête et du cou sur deux modèles murins, cette étude évalue les effets d'une radiothérapie pulsée à faible dose de rayonnements sur l'oxygénation de la tumeur
Purpose : To evaluate the efficacy of low-dose pulsed radiotherapy (PRT) in two head and neck squamous cell carcinoma (HNSCC) xenografts and investigate mechanism of action of PRT compared with standard radiotherapy (SRT). Methods and Materials : Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy x10 with 3-minute pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, 18F-FDG (tumor metabolism) and 18F-FMISO (hypoxia) PET imaging at pre-, mid-, and post-treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology. Results : UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared to UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia following SRT when compared to PRT as measured by 18F-FMISO PET. In contrast, no differences were seen in 18F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histological analysis of pimonidazole staining mimicked the 18F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors. Conclusions : Differences in 18F-FMISO uptake for UT14 tumors post-RT between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by 18F-FMISO and pimonidazole.
http://www.redjournal.org/article/S0360-3016(15)00375-2/abstract