I-124 Imaging and Dosimetry

Although radioactive iodine imaging and therapy are one of the earliest applications of theranostics, there still remain a number of unresolved clinical questions as to the optimization of diagnostic techniques and dosimetry protocols. I-124 as a positron emission tomography (PET) radiotracer has the potential to improve the current clinical practice in the diagnosis and treatment of differentiated thyroid cancer. The higher sensitivity and spatial resolution of PET/computed tomography (CT) compared to standard gamma scintigraphy can aid in the detection of recurrent or metastatic disease and provide more accurate measurements of metabolic tumor volumes. However the complex decay schema of I-124 poses challenges to quantitative PET imaging. More prospective studies are needed to define optimal dosimetry protocols and to improve patientspecific treatment planning strategies, taking into account not only the absorbed dose to tumors but also methods to avoid toxicity to normal organs. A historical perspective of I-124 imaging and dosimetry as well as future concepts are discussed

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments

A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comisión Nacional de Energía Atómica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient´s skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 ± 0.05 × 10(-21) A n(-1)[middle dot]cm² [middle dot]s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.Fil: Miller, Marcelo Eduardo. Comisión Nacional de Energía Atómica; ArgentinaFil: Sztejnberg, Manuel L.. Comisión Nacional de Energía Atómica; ArgentinaFil: González, Sara Josefina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; ArgentinaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Estryk, Guillermo. Comisión Nacional de Energía Atómica; Argentin

Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients’ images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT for HER2+ breast cancers for deep seated tumors using MITRII-FCB facility with an 8 cm diameter beam (port closest-to-tumor position), with boron concentrations in the tumor higher than 32 μg/g, and for a tumor-to-healthy tissue boron concentration ratio of 8:1. The therapeutic ratios for the proposed treatment would be higher than five for skin and adipose tissue and higher than three for tumor surrounding fibroglandular tissue. The microdosimetry study shows potential improvements in the therapeutic ratios based on the expected sub-cellular boron biodistributions. The engineering simulation study of clinical cases shows the advantages of using BNCT for HER+ breast cancers. Assuming an assured high efficiency of the boron agent delivery, the proposed concept can be considered for stage IV HER2+ breast cancers in treating the metastasized tumors in brain, head and neck, and lungs

Radiation shielding aspects for long manned mission to space: Criteria, survey study, and preliminary model

The prospect of manned space missions outside Earth's orbit is limited by the travel time and shielding against cosmic radiation. The chemical rockets currently used in the space program have no hope of propelling a manned vehicle to a far away location such as Mars due to the enormous mass of fuel that would be required. The specific energy available from nuclear fuel is a factor of 106 higher than chemical fuel; it is therefore obvious that nuclear power production in space is a must. On the other hand, recent considerations to send a man to the Moon for a long stay would require a stable, secured and safe source of energy (there is hardly anything beyond nuclear power that would provide a useful and reliably safe sustainable supply of energy). National Aeronautics and Space Administration (NASA) anticipates that the mass of a shielding material required for long travel to Mars is the next major design driver. In 2006 NASA identified a need to assess and evaluate potential gaps in existing knowledge and understanding of the level and types of radiation critical to astronauts' health during the long travel to Mars and to start a comprehensive study related to the shielding design of a spacecraft finding the conditions for the mitigation of radiation components contributing to the doses beyond accepted limits. In order to reduce the overall space craft mass, NASA is looking for the novel, multi-purpose and multi-functional materials that will provide effective shielding of the crew and electronics on board. The Laboratory for Neutronics and Geometry Computation in the School of Nuclear Engineering at Purdue University led by Prof. Tatjana Jevremović began in 2004 the analytical evaluations of different lightweight materials. The preliminary results of the design survey study are presented in this paper

Study of thermal scattering for organic tissues through molecular dynamics

Boron Neutron Capture Therapy (BNCT) is an experimental therapy for tumors which is based on the nuclear reaction that occurs when 10B is irradiated with thermal neutrons. Calculations for BNCT with Monte Carlo N-Particle (MCNP) take into account the thermal scattering treatment for hydrogen bound in bulk water for any organic tissue. However, in these tissues, hydrogen is also present in macromolecules (protein, lipids, etc.) and in confined water. Thermal scattering cross section for hydrogen in an organic tissue can be determined by calculating the scattering law S(α,β). This function can be obtained with the nuclear data processing system NJOY from the vibrational frequency spectrum of an atom in a molecular system. We performed calculations of the frequency spectrum from molecular dynamics simulations using the program GROMACS. Systems composed of a peptide in a water box were considered, with different proportions of water molecules. All-atom potentials for modeling this molecules were used in order to represent the internal vibrational normal modes for the atoms of hydrogen. The results showed several internal normal modes that in the case of hydrogen bound in bulk water do not appear

Study of thermal scattering for organic tissues through molecular dynamics

Boron Neutron Capture Therapy (BNCT) is an experimental therapy for tumors which is based on the nuclear reaction that occurs when 10B is irradiated with thermal neutrons. Calculations for BNCT with Monte Carlo N-Particle (MCNP) take into account the thermal scattering treatment for hydrogen bound in bulk water for any organic tissue. However, in these tissues, hydrogen is also present in macromolecules (protein, lipids, etc.) and in confined water. Thermal scattering cross section for hydrogen in an organic tissue can be determined by calculating the scattering law S(α,β). This function can be obtained with the nuclear data processing system NJOY from the vibrational frequency spectrum of an atom in a molecular system. We performed calculations of the frequency spectrum from molecular dynamics simulations using the program GROMACS. Systems composed of a peptide in a water box were considered, with different proportions of water molecules. All-atom potentials for modeling this molecules were used in order to represent the internal vibrational normal modes for the atoms of hydrogen. The results showed several internal normal modes that in the case of hydrogen bound in bulk water do not appear

Development of a prompt gamma neutron activation analysis facility for 10B concentration measurements at RA-3: Design stage

A PGNAA facility is being developed for 10B concentration measurements at RA-3 reactor. Its design targets detection limits better than tenths of microgram and irradiation times on the order of minutes. Computational models were developed, which estimated thermal neutron fluxes in irradiation position larger than 10^9 n·cm^(−2)s^(−1). Calculated amounts of photons and fast neutrons make necessary filter/moderator arrangements. An irradiation device was designed and numerically tested, which is being built and is to be used for performing characterizing measurements