Radionuclides and committed internal exposure dose for radioactivation in boron neutron capture therapy

1.1. Boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a particle therapy in which the neutron capture reaction of ¹⁰B compounds injected in human body is used to destroy tumour cells. Alpha particles and ⁷Li nuclei are emitted when ¹⁰B reacts with thermal neutrons. The ranges of the two emitted particles are significantly short and do not exceed the diameter of a typical cell. The cross-section of the (n,α) reaction of ¹⁰B is almost 2,000 times larger than that of the thermal neutron capture reaction with nitrogen which is a component of human tissue. If a compound with ¹⁰B accumulates selectively in tumour cells at a sufficient concentration, the selective destruction of the tumour cells can be estimated by neutron irradiation.

1.2. Internal dose exposure in BNCT

It is important to estimate the dose exposed to a patient’s normal tissues during radiotherapy. In particular, in BNCT, thermal and epithermal neutron irradiation are performed on the patient to ensure that the components constituting the body can be activated.

Several studies have used in-vivo activation experiments in animal models (Nakamura et al., 2017), simulation calculations (Sakurai et al., 2019), and clinical studies (Chun-Kai et al., 2021). These reports suggest that several radioactivation materials produced by thermal and epithermal neutron irradiation in BNCT contribute to internal exposure. In these reports, only the gamma ray was measured; therefore, the alpha and beta rays were not estimated. In addition, the dose estimates were inadequate because it was difficult to estimate blood activation in the simulation calculations. Therefore, it is necessary to consider these factors when estimating the internal radiation exposure.

1.3. Aims of this study

To evaluate the effects of internal exposure owing to the activation of the body in consideration of blood, it was compared to external exposure to evaluate the exposure dose more accurately.

2.1. Conditions of simulation calculation

Fig. 1 shows a flow chart of the radiation exposure estimation. Two simulation systems, namely, the Particle and Heavy Ion Transport System (PHITS) Ver.3.20 (Sato et al., 2018) and Dose and Risk Calculation Software (DCAL) Ver.9.4 (Eckerman et al., 2008), were used to estimate the radiation exposure. The standard epithermal neutron irradiation mode of the Heavy Water Neutron Irradiation Facility installed in the Kyoto University Research Reactor (KUR-HWNIF) was modelled as the BNCT irradiation field in a simulation (Sakurai and Kobayashi, 2000). Adult male and female models of the Korean standard-type calculation phantom, mesh-type reference Korean phantoms (MRKPs), were used as human phantoms in the PHITS (Choi et al., 2019). The ¹⁰B concentration in normal tissues and blood was set to 25 ppm, the KUR operation power was set to 5 MW, and the irradiation time was set to 1 h. Five irradiation areas in the head and neck regions were selected: the anterior neck, posterior neck, parietal, temporal, and occipital regions.

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Fig. 1.

Flow chart of radiation exposure estimation.

Because simulation calculations may not accurately model the effects of radiation attenuation, collimator diameter, thickness, and geometry, it is necessary to renormalise the calculation results based on the measured data. The measured data of thermal neutron flux at the beam centre axis of 20 cm in a cubic water phantom were obtained using the gold activation method in the standard epithermal neutron irradiation mode of KUR-HWNIF.

From the comparison between the measured data and calculated results, it was confirmed that the calculated values did not agree with the measured values, and renormalisation of the calculated values was necessary. However, the renormalised calculation results agreed with the measured data.

2.3. Radiation exposure estimation

The external exposure was estimated for comparison with the internal exposure. Radiation weighting factors were estimated by calculating the neutron energy spectra for each organ using PHITS. The tissue weighting factors in ICRP Publication 103 were used to estimate the exposure dose (ICRP, 2007). Gender-averaged equivalent doses were estimated from the equivalent doses for the male and female MRKPs using PHITS, and the gender-averaged effective dose was then estimated.

For internal exposure, the main radionuclides and the amount of radioactivity produced during irradiation were obtained using PHITS, excluding ultra-short half-life radionuclides, radionuclides with extremely low radioactivity, and spontaneous radionuclides. Subsequently, the coefficients for the committed equivalent and effective doses were determined based on the assumption that each radionuclide was distributed throughout the body via blood flow using DCAL. The committed equivalent and effective doses to the entire body were estimated from these coefficients.

3.1. Equivalent and effective dose for external exposure

Fig. 2 shows the equivalent and effective doses for the external exposure of the five irradiated parts. In the case of the irradiation for the anterior neck region, the effective dose owing to external exposure, including ‘Others’ comprising the irradiated volume and its surroundings, was 89 mSv on average for the whole body. However, excluding the region ‘Others’, the effective dose was 8.8 mSv. In addition, the dose for the region ‘Others’ accounted for a larger part of the effective dose for each irradiation part. The equivalent doses were highest in the region ‘Others’ on the order of 100 mSv. The equivalent doses for each organ in and around the irradiated volume were larger, ranging from 1 to 100 mSv. This suggests that external exposure originated in and around the irradiated volume.

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Fig. 2.

Equivalent and effective dose for external exposure for five irradiation parts.

Fig. 3 shows the radionuclides and radioactivity of the five irradiated parts. The 10 major radionuclides produced by activation were ²⁴Na, ²⁷Mg, ²⁸Al, ³¹Si, ³²P, ³⁸Cl, ⁴²K, ⁴⁹Ca, ⁴⁹Sc, and ¹²⁸I. The generated radioactivity, such as ³⁸Cl, ⁴⁹Ca, and ¹²⁸I, in the tissues, bones, teeth, and thyroid in and around the irradiated volume showed large values. In particular, for elements localised in specific organs, such as iodine in the thyroid gland, the amount of radioactivity produced is highly dependent on the irradiated part. Therefore, consideration of irradiation in treatment planning contributes to the reduction of radioactivation in specific organs, such as the thyroid gland.

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Fig. 3.

Radionuclides and radioactivity for five irradiation parts.

 Fig. 4 shows the committed equivalent and effective doses estimated from the generated radioactivity. In particular, the contribution of each radionuclide to the equivalent dose in each organ indicated that the effects of ²⁴Na, ³²P, and ¹²⁸I were significant, as shown in Fig. 3. ²⁴Na is uniformly present in the body because it is present in the tissues. The contribution of ³²P to the bone surface and red marrow was remarkable. This is related to the fact that ³²P is a bone seeker. ¹²⁸I is produced only in the thyroid; therefore, its effect depends on the irradiated part.

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Fig. 4.

Committed equivalent and effective dose for internal exposure for five irradiation parts.

The calculated effective dose to the anterior neck region is 7.9 mSv. This is one order of magnitude lower than that of the external exposure. Therefore, the internal exposure is not negligible for exposure dose estimation in BNCT. However, the effective dose can be relatively small depending on the irradiated part. Therefore, irradiation should be considered during treatment planning.