Experimental investigation of the characteristics of radioactive beams for heavy ion therapy

PURPOSE: This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether or not they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired post-irradiation using an in-beam whole-body positron emission tomography scanner for range verification quality assurance. METHODS: The energy deposited by monoenergetic beams of (11) C at 350 MeV/u, (15) O at 250 MeV/u, (12) C at 350 MeV/u and (16) O at 430 MeV/u were measured using a cruciform transmission ionisation chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose-mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon-on-insulator mushroom microdosimeter. Using the modi_ed microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the post-irradiation distributions of positron annihilations resulting from the decay of positron-emitting nuclei were measured for each beam in a gelatin phantom using the in-beam whole-body positron emission tomography scanner at HIMAC. The depth of maximum positron-annihilation density was compared with the depth of maximum dose deposition and the signal-to-background ratios were calculated and compared for images acquired over 5 minutes and 20 minutes post irradiation of the phantom. RESULTS: In the entrance region, the RBE10 was 1.2 +/- 0.1 for both (11) C and (12) C beams, while for (15) O and (16) O it was 1.4 +/- 0.1 and 1.3 +/- 0.1, respectively. At the Bragg peak, the RBE10 was 2.7 +/- 0.4 for (11) C and 2.9 +/- 0.4 for (12) C, while for (15) O and (16) O it was 2.7 +/- 0.4 and 2.8 +/- 0.4, respectively. In the tail region, RBE10 could only be evaluated for carbon; the RBE10 was 1.6 +/- 0.2 and 1.5 +/- 0.1 for (11) C and (12) C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal-to-background ratios compared to those obtained from targets irradiated by non-radioactive ion beams, with 5-fold and 11-fold increases in the ratios calculated for the (15) O and (11) C images compared with the values obtained for (16) O and (12) C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 +/- 0.8 mm for (11) C, compared to -5.6 +/- 0.8 mm for (12) C and 0.9 +/- 0.8 mm for (15) O versus -6.6 +/- 0.8 mm for (16) O. CONCLUSIONS: The RBE10 values for (11) C and (15) O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, (11) C and (15) O beams produce much better quality images for range verification compared with (12) C and (16) O, in particular with regards to estimating the location of the Bragg peak.