AN IODINE LABELED PORPHYRIN AS A NEW RADIATION SENSITIZER IN HUMAN BLADDER CANCER CELLS IN VITRO AND IN VIVO, COMBINING PHOTODYMAMIC THERAPY (PDT) WITH PHOTON ACTIVATION THERAPY (PAT)
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- Ishibashi Naoya
- Department of Radiology, Nihon University School of Medicine
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- Fujiwara Kyoko
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine
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- K. Pandey Ravindra
- Chemistry Division, PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, New York, United States
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- Kataba Motoaki
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine
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- Oguni Asako
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine
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- Igarashi Jun
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine
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- Soma Masayoshi
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine
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- Shizukuishi Takashi
- Department of Radiology, Nihon University School of Medicine
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- Maebayashi Toshiya
- Department of Radiology, Nihon University School of Medicine
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- Abe Katumi
- Department of Radiology, Nihon University School of Medicine
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- Abe Osamu
- Department of Radiology, Nihon University School of Medicine
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- Takahashi Motoichiro
- Department of Radiology, Nihon University School of Medicine
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- Tanaka Yoshiaki
- Institute of General Science, Nihon University
書誌事項
- タイトル別名
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- AN IODINE LABELED PORPHYRIN AS A NEW RADIATION SENSITIZER IN HUMAN BLADDER CANCER CELLS IN VITRO AND IN VIVO, COMBINING PHOTODYNAMIC THERAPY (PDT) WITH PHOTON ACTIVATION THERAPY (PAT)
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Purpose: 124Iodine-isotope labeled porphyrin pyropheophorbide HPPH (124I-HPPH) has been developed for photodynamic therapy (PDT) and positron emission tomography (PET) imaging. We hypothesize that HPPH with cold iodine (127I-HPPH, 717), which occurs as an intermediate product in 124I-HPPH synthesis, can act as a new specific and selective radiosensitizer, because iodine is used as a contrast agent in clinical X-ray imaging. The peak X-ray energy was set at 33keV (the K-edge absorption energy of iodine), with the advantages of both PDT and Photon Activation Therapy (PAT). In this study, we evaluated the radiosensitizing activity of 717 in a human bladder cancer cell line. Methods and Materials: The in vitro radiosensitization activity of 717 was tested in T24 human bladder cancer cell lines using the WST and colony formation assays. Subcellular localization of 717 was investigated using confocal microscopy with organelle probes and High Performance Liquid Chromatography (HPLC). Generation of reactive oxygen species (ROS) after 717 treatment combined with X-ray irradiation was measured by hydroxyl radical (OH.) detection using the fluorescence reagent 2-(6-(4-amino)phenoxy-3H-xanthen-3-on-9-yl) benzoic acid (APF). To evaluate the radiosensitizing effect of 717 in vivo, X-ray irradiation with or without prior injection of 717 was applied to mice treated with subcutaneous injection of T24 cells on their back. Results: T24 cells treated with 717 prior to radiation showed lower cell survival than cells irradiated without 717 treatment with the WST8 assay. In the colony formation assay, only treatment with 717 prior to radiation exhibited any radiosensitization effect. 717 was localized mainly in the Golgi apparatus and mitochondria. Under X-ray irradiation, APF with 717 showed a greater increase of fluorescence compared with APF without 717, indicating that 717 could generate ROS in response to X-ray irradiation. Conclusions: 717 can enhance tumor radiosensitivity based upon the WST and colony formation assays. Iodine may play a crucial role in the radiosensitizing activity of 717. The radiosensitizing effect of 717 may be caused by ROS generation following X-ray irradiation. 717 is oncotropic with minimal toxicity. Thus, utilization of 717 has a great advantage as a radiosensitizer.
収録刊行物
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- 日大医学雑誌
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日大医学雑誌 72 (4), 212-219, 2013
日本大学医学会
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詳細情報 詳細情報について
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- CRID
- 1390001206433647616
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- NII論文ID
- 10031195550
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- NII書誌ID
- AN0018408X
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- ISSN
- 18840779
- 00290424
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- NDL書誌ID
- 024866469
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
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