Matthias Müller1, Yimin Wang2, Michael R Squillante2, Kathryn D Held3, R Rox Anderson4, Martin Purschke5. 1. Wellman Center for Photomedicine, Massachusetts General Hospital/Harvard Medical School, Boston, United States. Electronic address: muller@mgh.harvard.edu. 2. Radiation Monitoring Devices, Inc., Watertown, United States. 3. Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, United States. 4. Wellman Center for Photomedicine, Massachusetts General Hospital/Harvard Medical School, Boston, United States. 5. Wellman Center for Photomedicine, Massachusetts General Hospital/Harvard Medical School, Boston, United States. Electronic address: mpurschke@mgh.harvard.edu.
Abstract
BACKGROUND AND PURPOSE: Radiation therapy is the gold standard treatment for inoperable malignant tumors. However, due to the heterogeneity of the tumor, some regions are more radio resistant and can lead to metastasis and tumor recurrence. In this study, we propose combining traditional X-ray treatment with UVC-emitting LuPO4:Pr3+ nanoparticles (NPs) to increase the tumor control as well as to reduce tumor recurrence and metastasis. These NPs convert ionizing radiation into UVC-photons (UVC range: 200-280 nm) locally at the tumor site. Unlike X-ray, UVC-photons damage DNA directly via an oxygen-independent mechanism, which could improve treatment of radioresistant tumors such as hypoxic tumors. MATERIALS AND METHODS: The effect of X-ray generated UVC-photons was tested on human fibroblasts incubated with NPs prior to radiation treatment. The surviving fraction of the cells was assessed by means of colony formation assay. Experiments were performed on normal and UVC sensitive cell lines to demonstrate the presence of UVC photons during treatment. In addition, UV-specific DNA damages were investigated using an immunofluorescence assay to measure cyclopyrimidine dimers (CPDs). RESULTS: Combined treatment showed an increased cell death of over 50%, compared to radiation alone. This results in a dose equivalent of 4 Gy for the combined treatment with 2 Gy irradiation. The formation of CPDs and the increased effect on UV sensitive cells indicate the presence of UV photons. The generated amount of CPDs is comparable to an UVC exposure of about 15 J × m-2. CONCLUSION: Combining NPs with ionizing radiation results in a localized dose surge, which could increase tumor control. It could also allow lowering the total applied dose to minimize unwanted side effects to the surrounding normal tissue while maintaining tumor control. Published by Elsevier B.V.
BACKGROUND AND PURPOSE: Radiation therapy is the gold standard treatment for inoperable malignant tumors. However, due to the heterogeneity of the tumor, some regions are more radio resistant and can lead to metastasis and tumor recurrence. In this study, we propose combining traditional X-ray treatment with UVC-emitting LuPO4:Pr3+ nanoparticles (NPs) to increase the tumor control as well as to reduce tumor recurrence and metastasis. These NPs convert ionizing radiation into UVC-photons (UVC range: 200-280 nm) locally at the tumor site. Unlike X-ray, UVC-photons damage DNA directly via an oxygen-independent mechanism, which could improve treatment of radioresistant tumors such as hypoxic tumors. MATERIALS AND METHODS: The effect of X-ray generated UVC-photons was tested on human fibroblasts incubated with NPs prior to radiation treatment. The surviving fraction of the cells was assessed by means of colony formation assay. Experiments were performed on normal and UVC sensitive cell lines to demonstrate the presence of UVC photons during treatment. In addition, UV-specific DNA damages were investigated using an immunofluorescence assay to measure cyclopyrimidine dimers (CPDs). RESULTS: Combined treatment showed an increased cell death of over 50%, compared to radiation alone. This results in a dose equivalent of 4 Gy for the combined treatment with 2 Gy irradiation. The formation of CPDs and the increased effect on UV sensitive cells indicate the presence of UV photons. The generated amount of CPDs is comparable to an UVC exposure of about 15 J × m-2. CONCLUSION: Combining NPs with ionizing radiation results in a localized dose surge, which could increase tumor control. It could also allow lowering the total applied dose to minimize unwanted side effects to the surrounding normal tissue while maintaining tumor control. Published by Elsevier B.V.
Entities:
Keywords:
Cancer treatment; Radiation therapy; Radiosensitizer; UV radiation
Authors: Suneil Jain; Jonathan A Coulter; Karl T Butterworth; Alan R Hounsell; Stephen J McMahon; Wendy B Hyland; Mark F Muir; Glenn R Dickson; Kevin M Prise; Fred J Currell; David G Hirst; Joe M O'Sullivan Journal: Radiother Oncol Date: 2014-01-17 Impact factor: 6.280