Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 µg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

A preliminary study of multispectral Cherenkov imaging and a Fricke-xylenol orange gel film (MCIFF) for online, absolute dose measurement.

BACKGROUND: Cherenkov luminescence imaging has shown potential for relative dose distribution and field verification in radiation therapy. However, to date, limited research utilizing Cherenkov luminescence for absolute dose calibration has been conducted owing to uncertainties arising from camera positioning and tissue surface optical properties. PURPOSE: This paper introduces a novel approach to multispectral Cherenkov luminescence imaging combined with Fricke-xylenol orange gel (FXG) film, termed MCIFF, which can enable online full-field absolute dose measurement. By integrating these two approaches, MCIFF allows for calibration of the ratio between two spectral intensities with absorbed dose, thereby enabling absolute dose measurement. METHODS: All experiments are conducted on a Varian Clinac 23EX, utilizing an electron multiplying charge-coupled device (EMCCD) camera and a two-way image splitter for simultaneous capture of two-spectral Cherenkov imaging. In the first part of this study, the absorbance curves of the prepared FXG film, which receives different doses, are measured using a fluorescence spectrophotometer to verify the correlation between absorbance and dose. In the second part, the FXG film is positioned directly under the radiation beam to corroborate the dose measurement capacity of MCIFF across various beams. In the third part, the feasibility of MCIFF is tested in actual radiotherapy settings via a humanoid model, demonstrating its versatility with various radiotherapy materials. RESULTS: The results of this study indicate that the logarithmic ratios of spectral intensities at wavelengths of 550 ± 50 and 700 ± 100 nm accurately reflect variations in radiation dose (R2 > 0.96) across different radiation beams, particle energies, and dose rates. The slopes of the fitting lines remain consistent under varying beam conditions, with discrepancies of less than 8%. The optical profiles obtained using the MCIFF exhibit a satisfactory level of agreement with the measured results derived from the treatment planning system (TPS) and EBT3 films. Specifically, for photon beams, the lateral distances between the 80% and 20% isodose lines, referred to as the penumbra (P80-20) values, obtained through TPS, EBT3 films, and MCIFF, are determined as 0.537, 0.664, and 0.848 cm, respectively. Similarly, for electron beams, the P80-20 values obtained through TPS, EBT3 films, and MCIFF are found to be 0.432, 0.561, and 0.634 cm, respectively. Furthermore, imaging of the anthropomorphic phantom demonstrates the practical application of MCIFF in real radiotherapy environments. CONCLUSION: By combining an FXG film with Cherenkov luminescence imaging, MCIFF can calibrate Cherenkov luminescence to absorbed dose, filling the gap in online 2D absolute dose measurement methods in clinical practice, and providing a new direction for the clinical application of optical imaging to radiation therapy.

Boron concentration prediction from Compton camera image for boron neutron capture therapy based on generative adversarial network.

Prompt gamma monitoring for the prediction of boron concentration is valuable for the dose calculation of boron neutron capture therapy (BNCT). This work proposes to use generative adversarial network (GAN) to predict the boron distribution based on Compton camera (CC) imaging quickly and provide a scientific basis for its application in BNCT. The BNCT and Compton imaging process was simulated, then the image reconstructed from the simulation and the contour of skin from CT are used as input, and the distribution of boron concentration from PET data is set as the output to train the network. The structural similarity, peak signal-to-noise ratio, and root mean square error of the images generated by the trained network are improved significantly, and the ratio of the boron concentration between the tumor area and the normal tissue is improved from 1.55 to 3.85, which is much closer to the true value of 3.52. The trained network can optimize the original image within 0.83 s, which is much faster than iterative optimization. The proposed method could help to ease the current online monitoring problem of boron concentration on a computational level, thereby promoting the clinical development of BNCT technology.

Proton range monitoring based on picosecond detection using a Cherenkov radiation detector: A Monte Carlo study.

In this study, we analyzed the performance of a PbF2 crystal-based detector at proton range monitoring with Monte Carlo simulations. The correlations between the depth-dose and Cherenkov profiles showed that the changes in the peak position in the Cherenkov profiles corresponded to the changes in the corresponding depth-dose profiles. Moreover, the deviations between the changes in the peak positions in the two curves were generally less than 2 mm. The results also showed that the actual proton range could be obtained using flight time information. When the proton energy was 160 MeV, the peak position detected in the Cherenkov profile detected was 14.83 cm with a flight time of 5.3-5.4 ns (starting from the time when protons were emitted), and the actual proton range in polymethyl-methacrylate was 15 cm. Therefore, the accuracy of the proton range measurements could be improved and the absolute range obtained by using the fast and time-sensitive characteristics of the proposed Cherenkov radiator.

Colocalization of tracks from boron neutron capture reactions and images of isolated cells.

In Boron Neutron Capture Therapy, the boronated drug plays a leading role in delivering a lethal dose to the tumour. The effectiveness depends on the boron macroscopic concentration and on its distribution at sub-cellular level. This work shows a way to colocalize alpha particles and lithium ions tracks with cells. A neutron autoradiography technique is used, which combines images of cells with images of tracks produced in a solid-state nuclear track detector.

Assessment of long-term risks of secondary cancer in paediatric patients with brain tumours after boron neutron capture therapy.

This study firstly explored the risks of secondary cancer in healthy organs of Chinese paediatric patients with brain tumours after boron neutron capture therapy (BNCT). Three neutron beam irradiation geometries (i.e. right lateral, top to bottom, posterior to anterior) were adopted in treating patients with brain tumours under the clinical environment of BNCT. The concerned organs in this study were those with high cancer morbidity in China (e.g. lung, liver and stomach). The equivalent doses for these organs were calculated using Monte Carlo and anthropomorphic paediatric phantoms with Chinese physiological features. The risk of secondary cancer, characterised by the lifetime attributable risk (LAR) factor given in the BEIR VII report, was compared among the three irradiation geometries. The results showed that the LAR was lower with the PA irradiation geometry than with the two other irradiation geometries when the 2 cm diameter tumour was at a depth of 6 cm on the right side of the brain. Under the PA irradiation geometry, the LAR in the organs increased with increasing tumour volume and depth because of the long irradiation time. As the patients aged from 10-15 years old, the LAR decreased, which was related to the increased patient height and shortened life expectancy. Female patients had a relatively higher risk of secondary cancer than male patients in this study, which could be due to the thinner body thickness and the weaker protective effect on the internal organs of the female patients. In conclusion, the risks of secondary cancer in organs were related to irradiation geometries, gender, and age, indicating that the risk of secondary cancer is a personalised parameter that needs to be evaluated before administering BNCT, especially in patients with large or deep tumours.

A Monte Carlo study of pinhole collimated Cerenkov luminescence imaging integrated with radionuclide treatment.

Cerenkov luminescence imaging (CLI) is an emerging optical imaging technique, which has been widely investigated for biological imaging. In this study, we proposed to integrate the CLI technique with the radionuclide treatment as a "see-and-treat" approach, and evaluated the performance of the pinhole collimator-based CLI technique. The detection of Cerenkov luminescence during radionuclide therapy was simulated using the Monte Carlo technique for breast cancer treatment as an example. Our results show that with the pinhole collimator-based configuration, the location, size and shape of the tumors can be clearly visualized on the Cerenkov luminescence images of the breast phantom. In addition, the CLI of multiple tumors can reflect the relative density of radioactivity among tumors, indicating that the intensity of Cerenkov luminescence is independent of the size and shape of a tumor. The current study has demonstrated the high-quality performance of the pinhole collimator-based CLI in breast tumor imaging for the "see-and-treat" multi-modality treatment.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT.

Investigation of the dose perturbation effect for therapeutic beams with the presence of a 1.5 T transverse magnetic field in magnetic resonance imaging-guided radiotherapy.

BACKGROUND: Magnetic resonance imaging (MRI)-guided radiotherapy is a promising image-guided cancer radiotherapy method. For MRI-guided radiotherapy, the proper energy of a therapeutic beam is important for beam-designing processes, and the magnetic-induced dose perturbation would be mainly influenced, especially the perturbation surrounding the tissue-air or air-tissue interfaces. Thus, it was necessary to investigate the impact of beam energy from photon, proton, and carbon ion beams on the magnetic-induced dose perturbations. MATERIALS AND METHODS: Using a phantom of a water-air-water structure, the dose distributions were calculated with or without the presence of a 1.5 T uniform magnetic field through GEANT4. Based on the calculated doses, magnetic-induced dose perturbations were then obtained. For investigating the effects of beam energies on magnetic-induced dose perturbations, low-, middle-, and high-beam energies were adopted for each beam type. RESULTS AND DISCUSSION: For photon beams, the dose perturbations were increased as the beam energies increased. At the up water-air interface, the maximum perturbations exceeded 50%. Near the edge of the radiation field, perturbations of 5%-20% were achieved. For proton and carbon ion beams, their Bragg peaks were shifted from original positions, and the shifting distances were increased with the increased beam energies. However, no evident magnetic-induced dose perturbations were noted at the up water-air interface and bottom air-water interface for all the beam energies. To some extent, this study provided references for assessing the effects of beam energies on magnetic-induced dose perturbations, especially the perturbations around the air cavities inside cancer patients. CONCLUSION: In MRI-guided cancer radiotherapy, the dose perturbation effects for therapeutic beams are relatively obvious, and the beam energies of therapeutic beams have large impacts on the magnetic-induced dose perturbations with the presence of a 1.5 T transverse magnetic field.

Measurement of dose in radionuclide therapy by using Cerenkov radiation.

This work aims to determine the relationship between Cerenkov photon emission and radiation dose from internal radionuclide irradiation. Water and thyroid phantoms were used to simulate the distribution of Cerenkov photon emission and dose deposition through Monte Carlo method. The relationship between Cerenkov photon emission and dose deposition was quantitatively analyzed. A neck phantom was also used to verify Cerenkov photon detection for thyroid radionuclide therapy. Results show that Cerenkov photon emission and dose deposition exhibit the same distribution pattern in water phantom, and this relative distribution relationship also existed in the thyroid phantom. Moreover, Cerenkov photon emission exhibits a specific quantitative relation to dose deposition. For thyroid radionuclide therapy, only a part of Cerenkov photon produced by thyroid could penetrate the body for detection; therefore, the use of Cerenkov radiation for measurement of radionuclide therapy dose may be more suitable for superficial tumors. This study demonstrated that Cerenkov radiation has the potential to be used for measuring radiation dose for radionuclide therapy.

Modulation of lateral positions of Bragg peaks via magnetic fields inside cancer patients: Toward magnetic field modulated proton therapy.

PURPOSE: This work investigated whether the Bragg peak (BP) positions of proton beams can be modulated to produce uniform doses and cover a tumor under the magnetic fields inside cancer patients, and whether magnetic field modulated proton therapy (MMPT) is effective in vital organ protection. METHODS: The authors initially constructed an ideal water phantom comprising a central tumor surrounded by cuboid organ regions using GEANT4. Second, we designed the proton beams passing through the gap between two adjacent organ regions during beam configuration. Third, we simulated the beam transports under magnetic fields inside the phantom through GEANT4. Then, the beams were discarded, which did not stop in the tumor. Fourth, the authors modulated the intensities of the remaining beams to produce uniform tumor doses. Subsequently, the calculated MMPT doses were compared with those of traditional methods, such as single, opposing, orthogonal, and box fields. Moreover, the authors repeated the above research procedures for abdominal anatomies comprising tumors at the pancreatic tail and liver to evaluate whether MMPT is effective for the human anatomy. RESULTS: For the water phantom, the vital organ doses were approximately 50%, 30%, 30%, and 15% for the single, opposing, orthogonal, and box fields, respectively. As the vital organ doses decreased, the organ volume receiving proton irradiations for the opposing, orthogonal, and box fields increased by two, two, and four times compared with that for the single field. The vital organ volume receiving proton irradiations were controlled to a fairly low level through MMPT, whereas the BP positions of the proton beams were properly modulated through the magnetic fields inside the phantom. The tumor was sufficiently covered by a 95% dose line, and the maximum tumor doses were smaller than 110%. For the pancreatic tumor case, the proton beams were curved and bypassed the kidney to generate uniform doses inside the tumor through MMPT. In the liver tumor case, the liver volume receiving proton irradiations was reduced by approximately 40% through MMPT compared with traditional methods. CONCLUSIONS: The BP positions can be intentionally modulated to produce uniform tumor doses under the magnetic fields inside cancer patients. In some special cases, the vital organs surrounding the tumor can almost be exempted from proton irradiations without sacrificing tumor dose coverage through MMPT. For the tumors inside parallel organs, the parallel organ volume receiving proton irradiations was largely reduced through MMPT. The results of this study can serve as beneficial implications for future proton therapy studies with reduced vital organ damage and complications.

Optimization of the Compton camera for measuring prompt gamma rays in boron neutron capture therapy.

Optimization of the Compton camera for measuring prompt gamma rays (0.478MeV) emitted during boron neutron capture therapy (BNCT) was performed with Geant4. The parameters of the Compton camera were determined as follows: 3cm thick - 10cm wide scatter detector (Silicon), 10cm thick - 10cm wide absorber detector (Germanium), and 1cm distance between the scatter and absorber detectors. For a typical brain tumor treatment, the overall detection efficiency of the optimized Compton camera was approximately 0.1425% using the Snyder's head phantom with a sphere tumor (4cm diameter and ~1cm depth).

Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

GEANT4 calculations of neutron dose in radiation protection using a homogeneous phantom and a Chinese hybrid male phantom.

The purpose of this study is to verify the feasibility of applying GEANT4 (version 10.01) in neutron dose calculations in radiation protection by comparing the calculation results with MCNP5. The depth dose distributions are investigated in a homogeneous phantom, and the fluence-to-dose conversion coefficients are calculated for different organs in the Chinese hybrid male phantom for neutrons with energy ranging from 1 × 10(-9) to 10 MeV. By comparing the simulation results between GEANT4 and MCNP5, it is shown that using the high-precision (HP) neutron physics list, GEANT4 produces the closest simulation results to MCNP5. However, differences could be observed when the neutron energy is lower than 1 × 10(-6) MeV. Activating the thermal scattering with an S matrix correction in GEANT4 with HP and MCNP5 in thermal energy range can reduce the difference between these two codes.

A Monte Carlo-based radiation safety assessment for astronauts in an environment with confined magnetic field shielding.

The active shielding technique has great potential for radiation protection in space exploration because it has the advantage of a significant mass saving compared with the passive shielding technique. This paper demonstrates a Monte Carlo-based approach to evaluating the shielding effectiveness of the active shielding technique using confined magnetic fields (CMFs). The International Commission on Radiological Protection reference anthropomorphic phantom, as well as the toroidal CMF, was modeled using the Monte Carlo toolkit Geant4. The penetrating primary particle fluence, organ-specific dose equivalent, and male effective dose were calculated for particles in galactic cosmic radiation (GCR) and solar particle events (SPEs). Results show that the SPE protons can be easily shielded against, even almost completely deflected, by the toroidal magnetic field. GCR particles can also be more effectively shielded against by increasing the magnetic field strength. Our results also show that the introduction of a structural Al wall in the CMF did not provide additional shielding for GCR; in fact it can weaken the total shielding effect of the CMF. This study demonstrated the feasibility of accurately determining the radiation field inside the environment and evaluating the organ dose equivalents for astronauts under active shielding using the CMF.

Calculations of S values and effective dose for the radioiodine carrier and surrounding individuals based on Chinese hybrid reference phantoms using the Monte Carlo technique.

The S values for the thyroid as the radioiodine source organ to other target organs were investigated using Chinese hybrid reference phantoms and the Monte Carlo code MCNP5. Two radioiodine isotopes (125)I and (131)I uniformly distributed in the thyroid were investigated separately. We compared our S values for (131)I in Chinese phantoms with previous studies using other types of phantoms: Oak Ridge National Laboratory (ORNL) stylized phantoms, International Commission on Radiological Protection (ICRP) voxel phantoms, and University of Florida (UF) phantoms. Our results are much closer to the UF phantoms. For each specific target organ, the S value for (131)I is larger than for (125)I in both male and female phantoms. In addition, the S values and effective dose to surrounding face-to-face exposed individuals, including different genders and ages (10- and 15-year-old juniors, and adults) from an adult male radioiodine carrier were also investigated. The target organ S values and effective dose for surrounding individuals obey the inverse square law with the distance between source and target phantoms. The obtained effective dose data in Chinese phantoms are comparable to the results in a previous study using the UF phantoms. The data generated in this study can serve as the reference to make recommendations for radiation protection of the Chinese patients or nuclear workers.