A characterization of dye gel dosimeters for boron neutron capture therapy - dose response to gamma rays

A three-dimensional verification method using dye gel dosimeters is studied for the external exposure in boron neutron capture therapy (BNCT). The characterization experiments of the dye gel dosimeters were performed for the dose response to gamma rays. As the dye gel dosimeters, leucomalite-green, leucocrystal-violet and genipin gels, which have different coloration characteristics, were selected. The results for the dose response to gamma rays showed linearity up to 100 Gy. However, it was found that the correction for auto-oxidation and dose rate dependency were necessary.


Introduction
In boron neutron capture therapy (BNCT) as well as the other radiotherapies, it is important to estimate the patient's exposure dose accurately from the viewpoint of radiation protection.The dose distribution near the target volume for treatment is estimated by simulation calculation using a treatment planning system.The external exposure can also be estimated by simulation calculation in the same way.However, no effective method has been established for the experimental verification of three-dimensional (3D) dose distribution.We are considering a method using gel dosimeters [1].
Gel dosimetry has been attracting attention as a method of external exposure dose estimation.The gel dosimeter is composed mainly of water as same as the human body.It is flexible and has a high degree of freedom in shape, which makes it possible to create a human equivalent phantom from the dosimeter itself.The gel dosimeter phantom after irradiation can be read by diagnostic devices such as MRI and CT to estimate the 3D dose distribution.
The BNCT irradiation field is a mixed field of thermal neutrons, epi-thermal neutrons, fast neutrons, and gamma rays, and the biological effectivenesses (RBEs) of these radiation components are different.It is necessary to discriminate the radiation components in the dose estimation.It is possible to create gel dosimeters with enhanced sensitivity for each radiation component by adjusting the ingredients.Although there are various types of gel dosimeters, dye gel dosimeters are attracting attention because they can be read by compact devices such as optical CT.By using a combination of dye gel dosimeters with different coloration characteristics and different sensitivities to the radiation components, the component-discrimination estimation can be expected.
We are studying a 3D verification method using dye gel dosimeters for the external exposure in BNCT.The characterization experiments of the dye gel dosimeters were performed mainly for the dose response to gamma rays.

Dye gel dosimeters
As the dye gel dosimeters for BNCT, micellar gel dosimeters with two organic dyes such as leucomalite-green (LMG) and leucocrystal-violet (LCV), and genipin gel dosimeter with genipin dye were selected.These gel dosimeters have the different characteristics for coloration [2], [3], [4].Using the combination of the coloration characteristics and the sensitization specific to the radiation components such as thermal neutrons, fast neutrons and gamma rays, the component-discrimination estimation by these gel dosimeters can be expected.To improve the sensitivity to thermal neutrons, boric acid was added to the LMG gel as a sensitizer.To decrease the sensitivity to fast neutrons, the genipin gel was prepared using heavy water instead of light water.
The materials and composition of the dye gel dosimeters are shown in Table 1.The prepared gels were poured into a PMMA cuvette (disposable cell) with 10 mm x 10 mm x 43 mm in inner volume and placed in an incubator at 4 degrees Centigrade for 1 hour for cooling and solidification.The light absorbance of the irradiated gel dosimeters was measured using a spectrophotometer (V730-Spectrophotometer, Japan Spectroscope Co., Ltd.).Table 1.The materials and composition of the dye gel dosimeters.* wt%: weight percentage.mM: millimolar (mol/m 3 ).** Since the leuco dye is insoluble in water, it is dispersed as micelles in an aqueous solution using a Tx-100: Triton X-100, surfactant.*** TCAA: Trichloroacetic acid is used for pH adjustment and it acts as a sensitizer.

Characterization for coloration by auto-oxidation
It has been reported that micellar gel colorates itself due to auto-oxidation [5].The experiment was performed for the coloration of micellar gels and fading of genipin gel due to auto-oxidation.The unirradiated gels were stored in an incubator at 4 degrees Centigrade for 1 day, and the coloration was confirmed for the gels at 1, 2, 4, 8 and 24 hours after the preparation.

Characterization for dose response to gamma rays
To characterize the dose response to gamma rays, the gels were irradiated with doses up to 100 Gy using Co-60 Gamma-ray Irradiation Facility at Institute for Integrated Radiation and Nuclear Science, Kyoto University.The light absorbance of the gel dosimeter immediately after the irradiation was measured by the spectrophotometer.Since the main component such as light water or heavy water affects the dose response of genipin gels, the differences in dose response were compared between light water and heavy water.Similarly, since additive dependency was reported, the differences in dose response of LMG gels were compared between additive and non-additive, such as added boric acid and non-additive [6].

Characterization for dose rate dependency
It has been reported that micellar gel dosimeter has the dependency for dose rate [7].The experiment was performed for the dose rate dependency.In the experiment, the dose rate was changed to 15, 30, 45, 60 and 75 Gy/h, and the irradiated dose was fixed to 60 Gy.The light absorbance of the irradiated gel dosimeters immediately after the irradiation was measured using the spectrophotometer.

Standard error and correction
Five measurement data of unirradiated gels, which were prepared and measured on the different days, were used for the estimation of the standard error after correcting for the effect of auto-oxidation.The changes of the light absorbance to gamma ray dose were re-estimated using the standard errors after correcting for the effects of auto-oxidation and dose rate dependence.

Characteristics for coloration by auto-oxidation
Figure 1 (a) shows the changes for the light absorbance due to auto-oxidation.Measurement wavelength were 600 nm for LCV gels and genipin gels, and 625 nm for LMG gels.The light absorbance of micellar gels such as LCV and LMG increases slightly during almost 24 hours.For genipin gel, the light absorbance decreases over time during almost 24 hours.

Characteristics for dose rate dependency
The changes of the light absorbance for the dose rate of gamma ray irradiation are shown in Figure 1 (b).The dependency for dose rate was confirmed for all the dye gel dosimeters.The genipin gel showed a high correlation by linear approximation and the micellar gels showed a high correlation by logarithmic approximation.

Characteristics for dose response to gamma rays
The light absorbance for the dose response corrected for the auto-oxidation and dose rate dependency are shown in Figure 1 (c).In this figure, the standard error was shown.Some data of LMG gel did not follow the approximate straight line.The dose response of the dye gels to gamma rays showed linearity up to 100 Gy, with strong correlation coefficients of R = 0.99 or more.For genipin and LMG gels, the color change could be clearly observed visually, while for LCV gels, only a slight change could be observed visually.

Influences for D 2O vs H2O and additive in gel
The light absorbance was almost two times larger for the genipin gel with light water than that with heavy water, as shown in Figure 1 (d).However, the linearity for the gamma ray dose was almost same for the both genipin gels.The coloration of the gel with the boric acid additive was smaller than non-additive when it was prepared, and the coloration rate was large.

Conclusion
It is considered that the correction for the effect of auto-oxidation and dose rate dependency using the approximate equation is necessary because the effect and dependency are large and not negligible.
It is difficult to confirm the color change visually and estimate the dose using the dye gel dosimeters under the same irradiation condition for BNCT clinical study, since the maximum dose is almost 10 Gy for normal tissue.The usability under the BNCT condition should be re-considered after the characterization for the response to neutrons and the dependency of linear energy transfer.
It was confirmed that there was no problem in the utilization of the genipin gel dosimeter with heavy water, and that the gel with the boric acid additive was more suitable for the measurement.The pH measurements for the gel dosimeters will be performed in future experiments.The standard error of genipin gel was larger than that of micellar gel.In addition to the weighting error during preparation, it is thought that the variation was larger due to the possibility that the dye was not uniform depending on the mixing conditions.For the response characteristics corrected for the auto-oxidation and the dose rate dependency with standard error, some data of LMG gel did not follow the approximate straight line.Considering this fact, the sensitivity was slightly greater at doses as low as 40 Gy for LMG gel.

Figure 1 .
Figure 1.The changes of the light absorbance