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Title: Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

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 [{sup 18}F]-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 similarmore » patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, 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.« less

Authors:
 [1]; ; ; ;  [2];  [1];  [3];  [1];  [3];  [3];  [4];  [3]; ;  [5];  [3];  [3];  [6];
  1. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)
  2. Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of)
  3. (Korea, Republic of)
  4. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of)
  5. Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)
  6. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States)
Publication Date:
OSTI Identifier:
22648716
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 3; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOMEDICAL RADIOGRAPHY; FLUORINE 18; FLUORINE COMPOUNDS; GY RANGE 10-100; IRRADIATION; LUNGS; MICE; NEOPLASMS; OPTIMIZATION; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; RADIOTHERAPY; SCHEDULES

Citation Formats

Song, Changhoon, Hong, Beom-Ju, Bok, Seoyeon, Lee, Chan-Ju, Kim, Young-Eun, Jeon, Sang-Rok, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Wu, Hong-Gyun, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Lee, Yun-Sang, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul, Cheon, Gi Jeong, Paeng, Jin Chul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Carlson, David J., and and others. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.01.064.
Song, Changhoon, Hong, Beom-Ju, Bok, Seoyeon, Lee, Chan-Ju, Kim, Young-Eun, Jeon, Sang-Rok, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Wu, Hong-Gyun, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Lee, Yun-Sang, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul, Cheon, Gi Jeong, Paeng, Jin Chul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Carlson, David J., & and others. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization. United States. doi:10.1016/J.IJROBP.2016.01.064.
Song, Changhoon, Hong, Beom-Ju, Bok, Seoyeon, Lee, Chan-Ju, Kim, Young-Eun, Jeon, Sang-Rok, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Wu, Hong-Gyun, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Lee, Yun-Sang, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul, Cheon, Gi Jeong, Paeng, Jin Chul, Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Carlson, David J., and and others. Fri . "Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization". United States. doi:10.1016/J.IJROBP.2016.01.064.
@article{osti_22648716,
title = {Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization},
author = {Song, Changhoon and Hong, Beom-Ju and Bok, Seoyeon and Lee, Chan-Ju and Kim, Young-Eun and Jeon, Sang-Rok and Cancer Research Institute, Seoul National University College of Medicine, Seoul and Wu, Hong-Gyun and Cancer Research Institute, Seoul National University College of Medicine, Seoul and Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul and Lee, Yun-Sang and Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul and Cheon, Gi Jeong and Paeng, Jin Chul and Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul and Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul and Carlson, David J. and and others},
abstractNote = {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 [{sup 18}F]-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 co-immunostaining, 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.},
doi = {10.1016/J.IJROBP.2016.01.064},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 95,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}