Studies on the effectiveness of dual radiosensitizers combined with radiation for the treatment of KHT sarcoma

• Main Author: 郭容妏
• Other Authors: 陳富都
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/89325487290023845798

碩士 === 國立陽明大學 === 放射醫學科學研究所 === 90 === Abstract Fractionation technique is generally employed in the conventional radiotherapy, however the tumor control rate usually depends on the tumor proliferation rate and fraction of hypoxic cells presented. Although both cycling-cell sensitizer and hypoxic-cell sensitizer are found to be useful in cell culture experiment, the combination of radiosensitizers with fractionated radiotherapy did not improve therapeutic effect significantly at the clinic. In recent years, the stereotactic radiosurgery technique has becoming an important technique in the treatment of benign or metastatic malignant tumors. This technique involves in the use of single large dose irradiation to the tumor target volume and hopefully to obtain better tumor control. This research aims at increasing metastatic lesion control probability by the combination of single irradiation with dual radiosensitizers. There are two types of cells in the malignant tumors, including cycling proliferative cells and resting hypoxic cells. Due to the fact that hypoxic cells have poor radiosensitivity, and that the normal tissue tolerance to the radiation has been limited. Hence, we proposed to increase tumor control probability by using dual radiosensitizers such as iododeoxyuridine (IUdR) and misonidazole (MISO) to combine with single large dose irradiation. In this study, we established KHT sarcoma animal model, then used in vivo-in vitro clonogenic assay system and tumor growth delay technique to evaluate tumor radiosensitization effect of the IUdR and MISO. By checking pharmacokinetic data obtained in a separate study, we have designed an optimal therapeutic strategy for the current research. The result demonstrated that the use of either IUdR or MISO combined with radiation has revealed a similar radiosensitization effect, the dose modification factor (DMF) for both groups was around 1.25, however, the dose modification factor was increased to 1.55 when both agents were combined with single irradiation. These results demonstrated that additive effect could be obtained by the combination of IUdR and MISO simultaneously with radiation. The result of current studies provided good choice for increasing the therapeutic effect of stereotactic radiosurgery. Looking forward to the future, we hope that the present finding can be extended to a clinical trail and eventually patients can be benefited by this approach.