Unraveling the mystery of enhanced cell-killing effect around the Bragg peak region of a double irradiation source 9C-ion beam

Abstract

An enhanced cell-killing effect at the penetration depths around the Bragg peak of a β-delayed particle decay 9 C-ion beam has been observed in our preceding radiobiological experiments in comparison with a therapeutic 12 C beam under the same conditions, and RBE values of the 9 C beam were revealed to be higher than those of the comparative 12 C beam by a factor of up to 2. This study is aimed at investigating the biophysical mechanisms underlying the important experimental phenomenon. First of all, a model for calculating the stopping probability density of the experimentally applied 9 C beam is worked out, where all determinants such as the initial momentum spread of the 9 C beam, the fluence attenuation with penetration depth due to the projectile-target nuclear reaction and the energy straggling effect are taken into account. On the basis of the calculated 9 C-ion stopping distribution, it has been found that the area corresponding to the enhanced cell-killing effect of the 9 C beam appears at the stopping region of the incident 9 C ions. The stopping 9 C-ion density in depth, then, is derived from the calculated probability density. Moreover, taking entrance dose 1 Gy for the 9 C beam as an example, the average stopping 9 C-ion numbers per cell at various depths are deduced. Meanwhile, the mean lethal damage events induced by the 9 C and comparative 12 C beams at the depths with almost equal dose-averaged LETs are derived from the measured cell surviving fractions at these depths for the 9 C and 12 C beams. Under the condition of the same absorbed doses, there are indeed good agreements between the average stopping 9 C-ion number pre cell and the difference of the mean lethal damage events between the 9 C and 12 C beams at the depths of similar dose-averaged LETs. It can be inferred that if a 9 C ion comes to rest in a cell, the cell would undergo dying. In view of the decay property of 9 C nuclide, clustered damage would be caused in the cell by the emitted low-energy particles. Therefore, the results achieved in this work can be taken as indirect evidence supporting that damage cluster is more efficient in leading to cell lethality.Clinical trials of heavy ion cancer therapy, especially carbon ion radiotherapy, have hitherto achieved unprecedented success against tumors resistant to conventional radiations and hard to cure with other modalities [1][2][3] . In the final analysis, the remarkable curative efficacy of the treatments with heavy ions is attributed to the inverted depth-dose distribution of the heavy ion beam and the elevated relative biological effectiveness (RBE) across the Bragg peak [4] . Radioactive ion beam provides a chance to spare the normal tissue as much as possible while increasing the effect of heavy ions on the focal region further. When applying a β-delayed particle decay 9 C beam to cancer therapy, the 9 C ion beam is a kind of double irradiation source, that is the external heavy-ion radiation itself and the delayed low-energy alpha particles and protons emitted internally [5][6...

Theoretical substantiation of biological efficacy enhancement for β‐delayed particle decay 9C beam: A Monte Carlo study in combination with analysis with the local effect model approach

“…Then, the local dose distribution could be determined according to Eq. (7). Subsequently, the value of expectation of DSB events n i in each integral element volume was obtained according to Eq.…”

“…7,8 The results showed that the RBE values for the 9 C beam were higher almost two times than those for the 12 C beam at the penetration depths around their Bragg peaks and the radioactive 9 C beam presented an enhanced cell-killing effect there. 7,8 Thus, it had been proposed that clustered damages in cells induced by the emitted low-energy particles result in such radiation effect enhancement. 7 However, both the detail of interactions between 9 C beam and cells and the specific process of clustered damage derivation need to be investigated to substantiate the speculation above.…”

“…The half-life of 9 C isotope is so long [126 ms (Ref. 7)] that most incident 9 C particles do not decay until their depositions. Therefore, radioactive 9 C beam can be regarded as a kind of double irradiation source, namely, the external heavy ion radiation itself and the delayed low-energy particles emitted internally, which lead to clustered damages in cells.…”

“…Therefore, radioactive 9 C beam can be regarded as a kind of double irradiation source, namely, the external heavy ion radiation itself and the delayed low-energy particles emitted internally, which lead to clustered damages in cells. 7 To explore the potential medical use of radioactive 9 C beam, cell radiobiological experiments using a 9 C beam and its counterpart 12 C beam were performed in the secondary beam line at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS), Japan. 7,8 The results showed that the RBE values for the 9 C beam were higher almost two times than those for the 12 C beam at the penetration depths around their Bragg peaks and the radioactive 9 C beam presented an enhanced cell-killing effect there.…”

“…7 To explore the potential medical use of radioactive 9 C beam, cell radiobiological experiments using a 9 C beam and its counterpart 12 C beam were performed in the secondary beam line at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS), Japan. 7,8 The results showed that the RBE values for the 9 C beam were higher almost two times than those for the 12 C beam at the penetration depths around their Bragg peaks and the radioactive 9 C beam presented an enhanced cell-killing effect there. 7,8 Thus, it had been proposed that clustered damages in cells induced by the emitted low-energy particles result in such radiation effect enhancement.…”