Radiobiological studies of high energy modulated proton beam

The radiobiological effects of 250 MeV protons on the normal skin and transplanted tumors of mice, C3H/He male, were compared with those of 180 kV X-rays for determining the relative biological effectiveness (RBE) and the therapeutic gain factor (TGF). There were no significant differences between protons and X-rays in the temporal developments of early skin reactions. From the dose-response curves of mean skin reactions for protons and X-rays, the RBE values of protons were obtained as 0.77, 0.79 and 0.87 for mean skin reaction scores of 1.5, 2.0 and 2.5, respectively. According to 2-fractionated experiments, the recovery dosis for protons corrected with the RBE were almost the same as those for X-rays. A fibrosarcoma which arose spontaneously in a C3H/Kam male mouse was used for the RBE studies of the tumor. From the dose-survival curves of tumor cells brought by the lung colony assay, the RBE values of protons were obtained as 0.94 and 0.95 at surviving fraction of 0.1 and 0.01. According to the tumor growth delay assay, RBE values were 0.81 and 0.77 for TGD15mm of 10 and 15 days. To estimate fibrotic changes of the skin, following two assays were performed. First one was quantitative analysis of the hydroxyproline content of the irradiated skin with the use of high-performance liquid chromatography. The other one was measurement of the collagen fiber area utilizing the image processing technique of photomicrographs. The RBE values were determined from dose-response curves at 24 weeks after irradiation. The RBE values of the hydroxyproline content were 0.75, 0.70 and 0.66 for the content of 85, 90 and 95 μg/mgDW, respectively. The RBE values of the collagen fiber area were 0.65, 0.65 and 0.70 for the area of 20, 25 and 30 %, respectively. While the TGF values normalized by the RBE of early skin reactions were ranging from 0.81 to 1.13, the TGF values normalized by the RBE of fibrotic changes of the skin were ranging from 1.01 to 1.25. (J.P.N.)