Carbon-ion radiation biological lethal dose distribution

Abstract

Background: Carbon-ion radiotherapy is an emerging modality used in cancer therapy. It has been very successful in treating solid cancers due to its excellent physical dose-distribution and deposition around the carbon-ion beam Bragg peak. Furthermore, its high-LET components allow for the treatment of tumors displaying radioresistance to low-LET radiotherapy modalities. Purpose: This present study was designed to investigate the biological range in which the carbon-ion beam irradiation distributes dosages resulting in significant cell death and how increases in initial dosage may impact this range. Furthermore, we sought to investigate how carbon-ion irradiation-induced genotoxicity may correlate with this biological range. Methods: Cellular lethality or genotoxicity via cell survival assays or cytokinesis-block micronucleus assays (CBMN), respectively, of monoenergetic 290 MeV/n carbon-ion beam irradiation were compared at increasing depths of CHO treated cells cultured in T-175 flasks. Cells were irradiated with initial dosages of either 1, 2 or 3 Gy for cell survival assays or an initial dosage of 1 Gy for CBMN assays. Following irradiation, cells were evaluated through survival fractions or micronuclei formation at specific depths, depending on the system. Results: Under all irradiation initial dosages of monoenergetic 290 MeV/n carbon-ion beams, survival fraction decreased as depth increased up to 14.5 cm. This depth was defined as our biologically observed Bragg peak due to there being few to no observable colonies. Following this depth there was a rapid increase in survival fraction at 15.0 cm. We observed survival fractions were most significantly reduced for the initial dosages of 1, 2 or 3 Gy between the ranges of 14.0 – 14.5, 13.5 – 14.5 and 12.5 – 14.5 cm (P < 0.0001), as well as, reappearance of colony formation occurring at the depths of 14.72, 14.77 and 14.78 cm, respectively. Micronuclei formation coincided with our cell survival assays treated with 1 Gy initial dosage, as micronuclei frequency increased as the depth increased up to 14.5 cm, indicative of an increased genotoxicity up to this depth. Conclusion: Monoenergetic 290 MeV/n carbon-ion beams with 1, 2 or 3 Gy initial dosages displayed a biologically observed Bragg peak at the depth of 14.5 cm and portrayed a biological lethal dose range of 0.72, 1.27 and 2.28 cm, respectively. Future Directions: Compare results obtained in this study with the clinically applicable carbon-ion spread-out Bragg peak (SOBP) technique to decipher if this technique induces the same cellular lethality. Compare results obtained in this study with the proton beam to decipher the degree in which the carbon-ion beam better distributes its lethal dosage. Enhance the efficiency in which the carbon-ion induces cell death via treatment of cells with a radiosensitizer.