Cell Survival in Spheroids Irradiated with Heavy-Ion Beams

Studies have been carried out with X rays and high-energy carbon and neon ion beams to evaluate high-LET cell survival in terms of RBE and possible contributions of intercellular communication. Comparisons were made of the postirradiation survival characteristics for cells irradiated as multicellular spheroids (approximately 100- and 300-μm diameters) and for cells irradiated in suspension. Comparison is made with 225-kVp X rays, 400 MeV/amu carbon ions, and 425 MeV/amu neon ions. X-Ray cell survival curves for cells from spheroids had larger$D_{0}\text{'}{\rm s}$than did the survival curve for cells grown in single-cell suspension. In addition, large spheroids did not have a detectable hypoxic cell fraction that would be evidenced by a radioresistant fraction in the cell survival curve. In the plateau region of the carbon beams the survival of cell suspensions and spheroid cells was not significantly different compared to X rays. At 10% survival the RBEs were 1.0 and 0.97, respectively, for cells irradiated in suspension and cells irradiated as spheroids. The spheroid cells continued to have larger D0values than cells from suspensions for the same radiation modality. Comparison of the effectiveness of the proximal, mid, and distal regions of the spread-out Bragg peak of carbon ions for cell killing in spheroids indicated that cell inactivation increased as a function of increasing LET. The survival dose relationship in the mid and distal peak regions was exponential, and the RBE, at 10% survival, was 1.9 and 2.1 compared to 1.5 for the proximal peak. Survival of single-cell suspensions and cells from large spheroids irradiated in the plateau region of neon was reduced slightly compared to X rays. As with plateau carbon ion, the spheroid cells exhibited greater radioresistance compared to the single-cell suspensions. Cell survival was the same for cells in suspension and spheroid cells in the neon proximal peak, and inactivation was exponential. The RBE values at 10% survival for suspension-grown cells and spheroid cells were 1.6 and 2.1. Examination of survival data for various regions in the spread Bragg peak of neon showed that a maximum RBE at 10% survival of 2.5 was found for the midpeak, while the lowest RBE value of 1.6 for neon was found for irradiation in the distal peak. We conclude that the higher average LET (200 keV/μm) in the distal peak region of the neon beam exceeds the maximally effective LET, which for this ion is probably below this val