Relative biological effectiveness (RBE) of 210Po alpha-particles versus X-rays on lethality in bovine endothelial cells

PURPOSE: Alpha-radiation from polonium-210 ((210)Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested (210)Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of (210)Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. MATERIALS AND METHODS: Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). RESULTS: Comparison of dose-response curves yielded RBE values of 13.1+/-2.5 (SEM) for cell viability, 10.3+/-1.0 for live cell number and 11.1+/-3.0 for LDH activity. The RBE values for clonogenic survival were 14.0+/-1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. CONCLUSIONS: Exposure to (210)Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.     

Relative biological effectiveness (RBE) of 210 Po alpha-particles versus X-rays on lethality in bovine endothelial cells

Purpose : Alpha-radiation from polonium-210 (210 Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested 210 Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of 210 Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. Materials and methods : Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). Results : Comparison of dose-response curves yielded RBE values of 13.1 ±2.5 (SEM) for cell viability, 10.3 ±1.0 for live cell number and 11.1 ±3.0 for LDH activity. The RBE values for clonogenic survival were 14.0 ±1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. Conclusions : Exposure to 210 Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.     

Relative biological effectiveness (RBE) of heavy ions (O+8) for producing retinal lesions.

The relative biological effectiveness (RBE) for oxygen ions (250 MeV/nucleon) for producing an ischemic retinal lesion in the rhesus monkey has been shown to be greater than 10. The RBE concept and the use of the standard methodology is discussed with respect to other published reports.     

Calculation of the relative biological efficiency (RBE) of neutron radiation

The Relative Biological Effectiveness (RBE) of radiation with different LET has to be recognized in the planning of radiation therapy especially if one type of radiation should be replaced by another type or if both should be used within the same irradiation course. In radiation therapy it is suitable to consider the RBE in connection with dose dependent cell survival rates. These rates can be described by means of corresponding mathematical models. A simple way to calculate the RBE on the basis of the modern LQ-model is demonstrated. In that procedure the alpha/beta-ratios which are known at least approximatively for many organs and tissues can be used. The proposed method is demonstrated for the human skin and lung. For these organs we obtained RBE ranges from 3.4 to 1.2 and from 3.8 to 0.8, respectively, considering increasing doses. Thereby, for the lung it can be observed that the dose dependency of the RBE for small doses is especially strong. The obtained results are in good coincidence with experiences in clinical practice.     

A comparison of methods to calculate biological effectiveness (RBE) from Monte Carlo simulations.

The relative biological effectiveness (RBE) of radiation is assessed and easily calculated by Monte Carlo simulations of the passage of radiation through matter. The expression to calculate the RBE provided by microdosimetry requires the use of the energy spectrum of charged particles. This paper compares the RBE values obtained for Palladium-103 (103Pd) and iodine-125 (125I) when calculated with 2 different spectra: the electron slowing-down spectrum and the ejection spectrum. The former yields a value of 10.6%, twice the value obtained with the latter (4.5%). Which spectrum to use is an open question. A theoretical argument is presented in favor of the ejection spectrum.     

Relative biological effectiveness of boron ions on human melanoma cells

Purpose : To compare the difference in relative biological effectiveness (RBE) between 10 B ions and a 60 Co γ-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. Materials and methods : Cells were irradiated in vitro under aerobic conditions with 60 Co and 10 B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm -1) . The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. Results : The RBE at 10% cell survival for 40, 80 and 160eV nm -1 boron ions compared with 60 Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. Conclusions : Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.     

Relative biological effectiveness of boron ions on human melanoma cells

PURPOSE: To compare the difference in relative biological effectiveness (RBE) between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. CONCLUSIONS: Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.     

Relative biological effectiveness (RBE) of p(26) + Be neutrons from the King Faisal Specialist Hospital and Research Centre CS-30 cyclotron measured by testis weight loss

Testis weight loss of C3H and Swiss-Webster (SW) mice was used as endpoint to determine the relative biological effectiveness (RBE) of p(26) + Be fast neutrons with respect to Co-60 gamma irradiation. Percent weight loss versus dose curves showed two components. Comparing first component effects, the RBE was 3.4 (C3H) and 3.7 (SW); when the second component was used, the RBE was 2.6 and 2.7 (C3H), and 3.5 (SW). When percent weight loss was plotted versus log dose, parallel lines were obtained, giving an RBE of 3.9 and 4.1 (C3H), and 4.2 (SW). Results were compared with published values and RBE as a function of fast neutron energy was plotted. A good correlation was found. Discrepancies seem to be mostly due to the use of different baseline radiation. When a constant correction is made, most of the values fit a single line. The possibility of using this approach as a substitute for international comparisons is discussed.     

The general relation between tissue response to x-radiation (alpha/beta-values) and the relative biological effectiveness (RBE) of protons: prediction by the Katz track-structure model

PURPOSE: Experimental data suggest that the relative biological effectiveness (RBE) of protons compared to x-rays may be determined by the alpha/beta-ratio of the x-ray survival curve. The data are referring to the centre of a spread-out Bragg peak (SOBP) formed to deliver a homogeneous dose to the tumour by modulating the proton energy. In an effort to explore the basis for this observation, calculations were performed to investigate the response of different biological targets through a range of proton energies and doses. MATERIALS AND METHODS: To describe the x-ray survival curve, the parameters of the linear-quadratic equation, alpha and beta, as well as those of the multi-target/single-hit equation, n and D0, were considered. These parameters were varied to investigate the RBE using the Katz track-structure model. Known cell line characterizations, as well as different hypothetical cells assuming different alpha/beta-ratios but similar target size parameters in the framework of the track-structure theory, were considered. RESULTS: The RBE was found to increase with increasing alpha/beta when the parameter n was varied, but to decrease with increasing alpha/beta when D0 was varied. This held when all other radiosensitivity parameters were assumed to stay constant. Thus, the RBE cannot be predicted by the alpha/beta-ratio alone. CONCLUSIONS: Although there is no direct correlation between the proton RBE and the parameters describing the x-ray survival curve, the track-structure model predicts a tendency for late-responding tissues (low alpha/beta) to have higher RBE values than early-responding tissues (high alpha/beta). These calculations reinforce the experimental findings, but also strongly suggest that there are circumstances in which the tendency for RBE to increase with increasing alpha/beta does not occur, or even could be reversed.     

Toxicity and relative biological effectiveness of alpha emitting radioimmunoconjugates

Radioimmunotherapy based on α-particle emitters has excellent properties as a treatment against micrometastatic and disseminated cancers because of the short path length (50 - 80 μm) and high linear energy transfer (～ 100 keV/ μm). Alpha-particles produce clustered DNA double-strand breaks and highly reactive hydroxyl radicals when hitting biological tissue. Hence, targeted α-particle therapy offers the potential of selective tumor cell killing with low damage to surrounding normal tissue. The ideal applications for targeted α-therapy are in treating neoplastic cells in circulation or when cancer cells are present as free-floating cells or spread along compartment walls. This review will provide a brief overview of the most promising radionuclides for targeted α-therapy and compare their relative biological effectiveness (RBE) and normal tissue toxicity.