The RBE-LET Relationship for Rodent Intestinal Crypt Cell Survival, Testes Weight Loss, and Multicellular Spheroid Cell Survival after Heavy-Ion Irradiation

Abstract

This report presents data for survival of mouse intestinal crypt cells, mouse testes weight loss as an indicator of survival of spermatogonial stem cells, and survival of rat 9L spheroid cells after irradiation in the plateau region of unmodified particle beams ranging in mass from 4He to 139La. The LET values range from 1.6 to 953 keV/microns. These studies examine the RBE-LET relationship for two normal tissues and for an in vitro tissue model, multicellular spheroids. When the RBE values are plotted as a function of LET, the resulting curve is characterized by a region in which RBE increases with LET, a peak RBE at an LET value of 100 keV/microns, and a region of decreasing RBE at LETs greater than 100 keV/microns. Inactivation cross sections (sigma) for these three biological systems have been calculated from the exponential terminal slope of the dose-response relationship for each ion. For this determination the dose is expressed as particle fluence and the parameter sigma indicates effect per particle. A plot of sigma versus LET shows that the curve for testes weight loss is shifted to the left, indicating greater radiosensitivity at lower LETs than for crypt cell and spheroid cell survival. The curves for cross section versus LET for all three model systems show similar characteristics with a relatively linear portion below 100 keV/microns and a region of lessened slope in the LET range above 100 keV/microns for testes and spheroids. The data indicate that the effectiveness per particle increases as a function of LET and, to a limited extent, Z, at LET values greater than 100 keV/microns. Previously published results for spread Bragg peaks are also summarized, and they suggest that RBE is dependent on both the LET and the Z of the particle.

Vulnerability of Feline T-Lymphocytes to Charged Particles

“…It is well established that at the same physical absorbed doses, high-LET heavy ions are more effective than low-LET radiations [3,5,9,16]. In line with this observation, we have shown that at the same physically absorbed doses, the RBE value for clonogenic survival and apoptosis incidence increased remarkably with an increase in LET over 16 keV/µm ( Figs.…”

Killing of Feline T-Lymphocytes by Gamma-Rays and Energetic Carbon Ions

“…Irradiation with carbon ions used in this study is expected to be most effective for cell killing, as it has been shown for human and rodent cells that RBE peaks at 100-200 keV/µm [1,3,8,22]. Carbon-ion irradiation significantly decreased the clonogenicity of FeT-J cells compared to γ-rays, as shown in Fig.…”

“…Moreover, by using a ridge filter, the Bragg peak can be spread out such that deep-seated tumors can be selectively irradiated with minimal exposure to surrounding normal tissues. In addition to this excellent selectivity of special dose distribution, heavy ions with a LET of 100-200 keV/µm are most effective for cell killing [1,3,8,22]. Furthermore, hypoxic cells within cancerous tissues, which are resistant to low-LET photons, can be effectively killed by high-LET heavy ions.…”

“…Irradiation with energetic carbon ions (114 keV/µm), of which LET has been known to maximize biological effects in human and rodent cells [1,3,8,22], exacerbated the killing of feline Tlymphocyte FeT-J cells with RBE of 2.98 relative to the D 10 dose of g-rays (0.2 keV/µm). Inactivation cross-section in cells exposed to carbon ions was 1691-fold higher than that in γ-irradiated cells (Fig.…”

“…High-LET radiations, including energetic heavy-ion particles, are more effective for cell killing [6,18,27] and apoptosis [20,24] than low-LET photons such as X-rays and γ-rays. Relative biological effectiveness (RBE) values reach a maximum at a LET of 100-200 keV/µm [1,3,8,22]. High-LET heavy ions have a more selective dose distribution as well as a higher RBE, and have been applied to radiotherapy in human patients for the treatment of malignant tumors in the lung [11], brain [12], liver [15], and prostate tissues [26]; this treatment has been shown to be more effective than therapy using conventional low-LET photons [25].…”