Masatoshi Hasegawa MD, Presenter: Nothing to Disclose

Takashi Nakano MD, Abstract Co-Author: Nothing to Disclose

Ken Yusa PhD, Abstract Co-Author: Nothing to Disclose

Yoshiyuki Suzuki, Abstract Co-Author: Nothing to Disclose

Hitoshi Ishikawa, Abstract Co-Author: Nothing to Disclose

Masaru Wakatsuki MD, Abstract Co-Author: Nothing to Disclose

Reiko Imai, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Purpose/Objective: The relative biological effectiveness (RBE) of heavy ion beams varies according to the cell or tissue type and the method of evaluation of the effectiveness, as well as the type, energy, dose, and frequency of radiation. The differences in the RBE values of heavy ion beams between normal tissues and tumors may have a great influence on the therapeutic ratio in practical radiation therapy. The purpose of this study was to evaluate and conduct a comparative analysis of the RBE values of carbon ion beams for radiation-induced apoptosis in radiosensitive normal tissues and radioresistant human tumors. Materials/Methods: The testes and small intestines of male C57BL/6 mice (8 weeks old), and two human tumors (a glioblastoma having mutant-type p53 and a primitive neuroectodermal tumor (PNET) having wild-type p53) transplanted into nude mice were irradiated with carbon ion beams (290 MeV/u, 6 cm spread-out Bragg peak) or 200 kV X-rays. The testes and the small intestines, as well as the tumors were histologically examined 4, 6, 9, 12, and 18 hours after 0.25-, 0.5-, 1-, 2-, or 4-Gy irradiation. Hematoxylin & eosin staining or TUNEL staining was performed to count the apoptotic cells. The incidence of apoptosis of the spermatogonia in stage 1-6 seminiferous tubules of the testes and of the crypt cells of the small intestines, as well as that in the tumors was examined. The time-courses of the changes in the prevalence of radiation-induced apoptosis and the dose-response curves for the peak incidence of apoptosis were evaluated, and the RBE values were estimated from the linear portion of those curves. Results: The prevalence of radiation-induced apoptosis of the spermatogonia peaked 9 hours after the irradiation (1.90/tubules after 1-Gy carbon-ion irradiation and 0.97/tubules after 1-Gy X-ray irradiation), whereas that of the crypt cells peaked 6 hours (2.1/crypt after 1-Gy carbon-ion irradiation and 1.2/crypt after 1-Gy X-ray irradiation). The estimated RBE values from the dose-response curves were 1.5 for the spermatogonia and 2.1 for the crypt cells. The prevalence of apoptosis in the glioblastoma and the PNET peaked 4-6 hours after the irradiation, although it was less in the glioblastoma than in the PNET. (glioblastoma; 0.67% after 1-Gy carbon-ion irradiation and 0.40% after 1-Gy X-ray irradiation. PNET; 1.65% after 1-Gy carbon-ion irradiation and 0.74% after 1-Gy X-ray irradiation). The RBE values for the tumors as estimated from the dose-response curves were 4.3 for the glioblastoma and 3.6 for the PNET. These values for the tumors were higher than those for the normal tissues. Conclusions: This study demonstrated that the RBE values of carbon ion beams for apoptosis of radiosensitive normal tissues are less than those for tumors having wild-type or mutant-type p53. The differences in the RBE values between radiosensitive normal tissues and tumors offer promise for a favorable therapeutic ratio in radiation therapy.

Hasegawa, M, Nakano, T, Yusa, K, Suzuki, Y, Ishikawa, H, Wakatsuki, M, Imai, R, et al, , Relative Biological Effectiveness (RBE) of Carbon Ion Beams for Apoptotic Cell Death: Comparison of Normal Tissues and Tumors.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4417952.html