The real-time tumor oxygenation changes following a single high dose radiotherapy in orthotopic and subcutaneous lung cancers in mice: clinical implication for stereotactic ablative radiotherapy schedule optimization
SCIE
SCOPUS
- Title
- The real-time tumor oxygenation changes following a single high dose radiotherapy in orthotopic and subcutaneous lung cancers in mice: clinical implication for stereotactic ablative radiotherapy schedule optimization
- Authors
- Changhoon Song; Beom-Ju Hong; Seoyeon Bok; Chan-Ju Lee; Kim, YE; Sang-Rok Jeon; Hong-Gyun Wu; Yun-Sang Lee; Gi Jeong Cheon; Jin Chul Paeng; David J Carlson; Hak Jae Kim; Ahn, GO
- Date Issued
- 2016-07-01
- Publisher
- Elsevier
- Abstract
- Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [F-18]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day -1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 +/- 0.483 at day -1, 1.67 +/- 0.116 at day 0, 2.92 +/- 0.334 at day 2, and 2.13 +/- 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 coimmunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased slightly by day 6. Our results indicate that single high-dose irradiation can produce a rapid, but reversible, vascular collapse in tumors. (C) 2016 Elsevier Inc. All rights reserved.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/36469
- DOI
- 10.1016/j.ijrobp.2016.01.064
- ISSN
- 0360-3016
- Article Type
- Article
- Citation
- International Jornal of Radiation Oncology, Biology, Physics, vol. 95, no. 3, page. 1022 - 1031, 2016-07-01
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