Computational Modeling of Cellular Effects Post-Irradiation with Low- and High-Let Particles and Different Absorbed Doses

Abstract

The use of computational methods to improve the understanding of biological responses to various types of radiation is an approach where multiple parameters can be modelled and a variety of data is generated. This study compares cellular effects modelled for low absorbed doses against high absorbed doses. The authors hypothesized that low and high absorbed doses would contribute to cell killing via different mechanisms, potentially impacting on targeted tumour radiotherapy outcomes. Cellular kinetics following irradiation with selective low- and high-linear energy transfer (LET) particles were investigated using the Virtual Cell (VC) radiobiology algorithm. Two different cell types were assessed using the VC radiobiology algorithm: human fibroblasts and human crypt cells. The results showed that at lower doses (0.01 to 0.2 Gy), all radiation sources used were equally able to induce cell death (p>0.05, ANOVA). On the other hand, at higher doses (1.0 to 8.0 Gy), the radiation response was LET and dose dependent (p<0.05, ANOVA). The data obtained suggests that the computational methods used might provide some insight into the cellular effects following irradiation. The results also suggest that it may be necessary to re-evaluate cellular radiation-induced effects, particularly at low doses that could affect therapeutic effectiveness.

Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting

“…In solid tumors the diffusion-limited penetration depths of radionuclide carriers [1][2][3] combined with the short range of α-particles (40-100 µm) [4] hamper their use mostly due to partial tumor irradiation. Given the high killing efficacy of α-particles (4-5 tracks across the nucleus result in cell kill) [5][6][7][8][9][10][11] which is also mostly independent of celloxygenation state unlike β-particles [12] this is quite unfortunate. Carrier molecules that diffuse substantially from the vasculature into the viable tumor have been suggested to be necessary for effective irradiation of the viable solid tumor-cell regions [3].…”