Increase in Tumor Oxygenation and Potentiation of Radiation Effects Using Pentoxifylline, Vinpocetine and Ticlopidine Hydrochloride

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概要

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• The purpose of the present study was to investigate the effects of Pentoxifylline (PTX), Vinpocetine (VPT) and Ticlopidine Hydrochloride (TCD), used commonly for vascular disorders in humans, on the pO_2 in SCCVII tumors of C3H/HeJ mice and on the radioresponse of SCCVII tumors. The pO_2 in the SCCVII tumors, which were measured 30 min after intraperioneal (i.p.) injection of PTX (5 mg/kg), VPT (5 mg/kg), or TCD (10 mg/kg) using polarography, was compared to that in saline-treated control tumors. All the three drugs, PTX, VPT and TCD, yielded significant increase of the pO_2 in the SCCVII tumors from 25.6 to 26.9 mmHg, from 18.6 to 22.9 mmHg, and from 22.6 to 25.9 mmHg, respectively. Frequency histogram of the pO_2 distribution in the saline-treated SCCVII tumors did not show hypoxic fraction of less than 10 mmHg. The radioresponses of the drugs were investigated by tumor growth delay assay. In the drug-treated groups, the SCCVII tumors were irradiated with a single dose of 15 Gy 30 min after injection of the drugs at the same doses as those used in the experiments for intratumoral pO_2 measurement. Compared with the irradiation alone group, significant tumor growth delays were observed in all the drug-treated groups. The time required to reach a four-fold increase in the initial tumor volume were 4 days in the saline-treated control group, 22 days in the irradiation (IR) alone group, 28 days in the PTX+IR group, 29 days in the VPT+IR group, and 32 days in TCD+IR group. In conclusion, VPT and TCD are potentially promising drugs for increasing the intratumoral pO_2 although the mechanism for radiopotentiation observed in the present study is unknown due to small hypoxic fraction in the SCCVII tumors. Further studies on other mechanisms for radiopotentiation of PTX, VPT or TCD, besides of increasing the pO_2 in the tumor, are needed.

• 日本放射線影響学会の論文
• 2005-12-28

著者

• SUZUKI Minoru

  Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University

• Suzuki M

  Particle Radiation Oncology Research Center Kyoto University

• HASEGAWA Takeo

  Med. Image and Info. Graduate School of Suzuka Univ. of Med. Sci.

• Hasegawa T

  Ehime Univ. Ehime

• Hasegawa Takeo

  Department of Surgery 1, Fukushima Medical University

• Hasegawa Takeo

  Department Of Radiological Technology Suzuka University Of Medical Science

• Hasegawa Takeo

  Department Of Materials Science Faculty Of Engineering Miyazaki University

• Suzuki Masao

  National Inst. Radiological Sci. Chiba Jpn

• Monzen Hajime

  Department of Cardiology, Otsu Red Cross Hospital

• Monzen Hajime

  Department Of Radiology Ohtsu Red Cross Hospital

• Monzen Hajime

  Department Of Cardiology Otsu Red Cross Hospital

• Hasegawa T

  Department Of Physics Faculty Of Science Kyoto University

• Ando Satoshi

  Department Of Radiation Oncology University Of Maryland Medical System

• Amano Morikazu

  Department Of Radiology Kakegawa City General Hospital

• TERAI Kaoru

  Department of Therapeutic Radiology - Radiation Oncology, University of Minnesota Academic Health Ce

• ANDOH Satoshi

  Radiation Oncology Department, University of Maryland Medical System

• TSUMURAYA Akio

  Graduate School of Health Science, Suzuka University of Medical Science

• Tsumuraya Akio

  Graduate School Of Health Science Suzuka University Of Medical Science

• Hasegawa Takeo

  Department Of Cardiothoracic Surgery Sapporo Medical University School Of Medicine

• Suzuki Minoru

  Particle Oncology Research Center Research Reactor Institute Kyoto University

• Terai Kaoru

  Department Of Therapeutic Radiology - Radiation Oncology University Of Minnesota Academic Health Cen

• Hasegawa T

  Miyazaki Univ. Miyazaki Jpn

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