Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

Navigating through the coordination preferences of heavy alkaline earth metals: Laying the foundations for 223Ra- and 131/135mBa-based targeted alpha therapy and theranostics of cancer.

The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted. This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV-Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.

Charting the Course of Targeted α Therapy With First-in-Human, Postadministration Image-Guided Dosimetry and Response Assessment of 212 Pb-VMT-α-NET in Metastatic Neuroendocrine Tumors.

ABSTRACT: 212 Pb emerges as a compelling in vivo α-particle generator for targeted α therapy due to its favorable half-life ( t1/2 = 10.6 hours) aligning with the biological half-lives of small peptides and its potent α-particle emissions within the decay series. However, one of the challenges with 212 Pb is to perform appropriate image-guided dosimetry. To date, all the data have been extrapolated from its imaging analog, 203 Pb. We present the first-in-human posttherapy image-guided dosimetric estimates of a single cycle of 212 Pb VMT-α-peptide, administered in a 41-year-old woman with an advanced grade 2 NET. The patient also demonstrated partial response on treatment.

Selection of radionuclide(s) for targeted alpha therapy based on their nuclear decay properties.

Targeted alpha therapy (TAT) is a promising form of oncology treatment utilising alpha-emitting radionuclides that can specifically accumulate at disease sites. The high energy and high linear energy transfer associated with alpha emissions causes localised damage at target sites whilst minimising that to surrounding healthy tissue. The lack of appropriate radionuclides has inhibited research in TAT. The identification of appropriate radionuclides should be primarily a function of the radionuclide's nuclear decay properties, and not their biochemistry or economic factors since these last two factors can change; however, the nuclear decay properties are fixed to that nuclide. This study has defined and applied a criterion based on nuclear decay properties useful for TAT. This down-selection exercise concluded that the most appropriate radionuclides are: 149 Tb, 211 At/ 211 Po, 212 Pb/ 212 Bi/ 212 Po, 213 Bi/ 213 Po, 224 Ra, 225 Ra/ 225 Ac/ 221 Fr, 226 Ac/ 226 Th, 227 Th/ 223 Ra/ 219 Rn, 229 U, 230 U/ 226 Th, and 253 Fm, the majority of which have previously been considered for TAT. 229 U and 253 Fm have been newly identified and could become new radionuclides of interest for TAT, depending on their decay chain progeny.

Formation mechanism of α particles in glycogen: Testing the budding hypothesis by Monte-Carlo simulation.

Glycogen, a complex branched glucose polymer and a blood-sugar reservoir in animals, comprises small ß particles joined together into composite α particles. In diabetic animals, α particles fragment more easily than those in healthy animals. Finding evidence for or against postulated mechanisms for α-particle formation is thus important for diabetes research. Insight into this is obtained here using Monte-Carlo simulations, including addition and loss of glucose monomer, branching and debranching, based on earlier simulations which were in acceptable agreement with experiment [Zhang et al., Int J Biol Macromolecules 2018, 116, 264]. One postulated mechanism for α-particle formation is "budding": occasionally a glucan chain temporarily protrudes from the particle, and if its growing end is sufficiently far from its parent particle, it propagates to a new linked particle. We tested this by simulations in which an "artificial" bud (a chain extending well outside the average particle radius) is added to a glycogen molecule in a dynamic steady state, and the system allowed to evolve. In some simulations, the particle reached a new steady state having an irregular dumbbell shape: a rudimentary α particle. Thus 'budding' is a possible mechanism for α particles to form. If no simulations had shown this behaviour, it would have refuted the postulate.

Current Status of Prostate-specific Membrane Antigen-targeted Alpha Radioligand Therapy in Prostate Cancer.

Prostate cancer (PCa) is the most prevalent malignancy and leading cause of mortality in men. Despite the development of various drugs, such as novel androgen receptor signaling inhibitors and poly adenosine diphosphate-ribose polymerase inhibitors targeting homologous recombination repair-related genetic mutations, prognosis of metastatic castration-resistant prostate cancer remains unfavorable. However, recent advances in nuclear medicine have allowed for both imaging diagnostics and therapeutic interventions by targeting molecules specifically expressed in cancer cells with radioisotopes (RI). γ-rays are used in nuclear medicine imaging, whereas in therapy, α or ß-emitting RIs are administered to target cells in radiation therapy. PCa, in particular, exhibits the characteristic features of radioligand therapy, as the membrane protein prostate-specific membrane antigen (PSMA) is proportionally highly expressed in malignancy compared to normal tissues. The administered RI-labeled compound binds to PSMA, enabling specific targeting of PCa for treatment. Unlike ß-rays, α-rays have a shorter range and impart stronger energy to DNA, allowing α-particles to exhibit a higher linear energy transfer. Due to such characteristics, PSMA-targeted α radiotherapy is expected to have potent cytotoxic effects and fewer side effects on normal organs, making them more likely to be widely adopted in the future. However, reports on PSMA-targeted α radiotherapy differ in aspects, such as prior PSMA-targeted ß radiotherapy, the administered doses, and the number of treatment cycles. Therefore, in this review, we compile the reports on treatments utilizing α-emitting isotopes targeting PSMA in patients with PCa.

Using spectroscopic autoradiography of alpha particles for the quantitative mapping of 226Ra ultra-traces in geo-materials.

The measurement of 226Ra and the identification of 226Ra-bearing minerals are important for studying the behavior of radium in the environment. Various instruments for measuring 226Ra are currently used: among the radiometric techniques that measure in bulk (no spatialization), there are gamma spectrometers and alpha spectrometers. Other instruments such as SEM-EDS can map the chemical elements thus providing information on the distribution of 226Ra, but are limited for ultra-trace analyses on natural geomaterials. Finally, autoradiography techniques can locate radioactivity, but are limited to the identification of the contribution of 226Ra when the 238U series is complete. This study focuses on spectroscopic autoradiography, a method for measuring both the energy of the alpha particle emissions and their positions on the autoradiograph. A gas detector based on a parallel ionization multiplier technology was used for this purpose. Alpha particle energy is dependent on the emitting radionuclides. In order to track the 226Ra, the energy spectrum of the 238U series was studied with modeling software. It appears possible to apply a thresholding on the energy spectrum to discriminate the 226Ra from the first alpha emitters of the 238U decay chain (i.e. 238U, 234U and 230Th, all below 5 MeV). The developed method was applied to a U-mill tailing sample prepared as a thin section. The sample was heterogeneous in terms of radioactivity and was not at secular equilibrium with 238U, as expected. The 226Ra was identified and localized, and different regions of interest were also analyzed with SEM-EDS elements cartography. This revealed 226Ra-rich barite (BaSO4) phases measured at 3 ppmRa on average and containing no uranium; and uranium in siderite (FeCO3), showing a strong 226Ra deficit compared with secular equilibrium. Spectroscopic autoradiography opens up possibilities for the analysis of heterogeneous geological samples containing natural alpha emitters such as 238U and 226Ra: the 226Ra can be localized and quantified at ultra-trace content, and the method developed can also identify newly (young) uranium phases by measuring 238U/226Ra activity disequilibrium.

Characterization of a segmented printed circuit board (PCB) as a standard for absorbed dose to water from alpha-emitting radionuclides.

BACKGROUND: Our previous work introduced and evaluated a standard for surface absorbed dose rate per unit radioactivity to water from unsealed alpha-emitting radionuclides used in targeted radionuclide therapy (TRT). An overall uncertainty over 4.0% at k = 1 was reported for the absorbed dose to air measurements, which was partially attributed to the rotational alignment uncertainty in the geometrical setup. PURPOSE: A printed circuit board (PCB) with a segmented guard was constructed to align the extrapolation chamber (EC) and the source plates using a differential capacitance technique. The PCB EC aimed to enhance the repeatability of the ionization current measurements. The PCB EC was evaluated using a thin film 210Po source. The measured absorbed dose to air cavity was compared with the Monte Carlo (MC) calculations. Using the extrapolation method, the surface absorbed dose rate to water was calculated. METHODS: The PCB EC was constructed with a 4.50 mm diameter collector surrounded by four sectors and a guard electrode. The sectors were isolated for rotational alignment and later connected to the guard for ionization current measurements. A bridge circuit measured differential capacitance between opposing sectors, and a hexapod motion stage rotated the source substrate to minimize the differential capacitance. The EC was evaluated using a 210Po source with a 3.20 mm diameter and 1.253 µ $\mu $ Ci radioactivity. MC simulations were performed to calculate the k p o i n t ${k}_{point}$ , k b a c k s c a t t e r ${k}_{backscatter}$ , and k d i v ${k}_{div}$ correction factors. Ionization current measurements were performed for air gaps in the 0.3-0.525 mm range and surface absorbed dose rate to water was calculated. RESULTS: Rotational offsets of up to 3.0° were found and the current repeatability was found to increase with the absorbed dose to air uncertainty calculated to be ∼2.0%. Using the capacitance method, the effective EC diameter was measured to be 4.53 mm. The recombination, polarity, and electrometer corrections were reported to be within 1.00% across all measurement trials. The MC-calculated correction factors were calculated to be much larger than the recombination and polarity correction factors. The average k p o i n t ${k}_{point}$ , k b a c k s c a t t e r ${k}_{backscatter}$ , and k d i v ${k}_{div}$ corrections were calculated to be 1.063, 0.9402, and 2.136, respectively. The MC-calculated absorbed dose to air was found to overestimate the absorbed dose by over 4.00% when compared with the measured absorbed dose to air. The surface absorbed dose rate to water was calculated to be 2.304 × 10 - 6 $2.304 \times {10}^{ - 6}$ Gy/s/Bq with an overall uncertainty of 4.07%. CONCLUSIONS: The constructed PCB EC was deemed suitable as an absorbed dose standard. A repeatable rotational alignment was achieved using the differential capacitance technique. The metal electrodes on the PCB made a difference of < 1.00% on the backscatter correction when compared to the EC comprised of polystyrene-equivalent collector. A 20% difference in the surface absorbed dose rate to water was found between the two ECs, which is attributed to the cavity diameter differences leading to different magnitudes of dose fall-off along the lateral direction.

A diffusion-leakage model coupled with dose point kernels (DPK) for dosimetry of diffusing alpha-emitters radiation therapy (DaRT).

BACKGROUND: Diffusing alpha-emitters radiation therapy (DaRT) is a novel brachytherapy technique that leverages the diffusive flow of 224Ra progeny within the tumor volume over the course of the treatment. Cell killing is achieved by the emitted alpha particles that have a short range in tissue and high linear energy transfer. The current proposed absorbed dose calculation method for DaRT is based on a diffusion-leakage (DL) model that neglects absorbed dose from beta particles. PURPOSE: This work aimed to couple the DL model with dose point kernels (DPKs) to account for dose from beta particles as well as to consider the non-local deposition of energy. METHODS: The DaRT seed was modeled using COMSOL multiphysics and the DL model was implemented to extract the spatial information of the diffusing daughters. Using Monte-Carlo (MC) methods, DPKs were generated for 212Pb, 212Bi, and their progenies since they were considered to be the dominant beta emitters in the 224Ra radioactive decay chain. A convolution operation was performed between the integrated number densities of the diffusing daughters and DPKs to calculate the total absorbed dose over a 30-day treatment period. Both high-diffusion and low-diffusion cases were considered. RESULTS: The calculated DPKs showed non-negligible energy deposition over several millimeters from the source location. An absorbed dose >10 Gy was deposited within a 1.8 mm radial distance for the low diffusion case and a 2.2 mm radial distance for the high diffusion case. When the DPK method was compared with the local energy deposition method that solely considered dose from alpha particles, differences above 1 Gy were found within 1.3 and 1.8 mm radial distances from the surface of the source for the low diffusion and high diffusion cases, respectively. CONCLUSIONS: The proposed method enhances the accuracy of the dose calculation method used for the DaRT technique.

Targeted Radium Alpha Therapy in the Era of Nanomedicine: In Vivo Results.

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes-Radium-223 and Radium-224 (223/224Ra)-in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting. To exploit the therapeutic gains of Ra across a wider spectrum of cancers, nanoparticles have recently been embraced as carriers to ensure the linkage of 223/224Ra to target-affine vectors. Exemplified by prior findings, Ra was successfully bound to several nano/microparticles, including lanthanum phosphate, nanozeolites, barium sulfate, hydroxyapatite, calcium carbonate, gypsum, celestine, or liposomes. Despite the lengthened tumor retention and the related improvement in the radiotherapeutic effect of 223/224Ra coupled to nanoparticles, the in vivo assessment of the radiolabeled nanoprobes is a prerequisite prior to clinical usage. For this purpose, experimental xenotransplant models of different cancers provide a well-suited scenario. Herein, we summarize the latest achievements with 223/224Ra-doped nanoparticles and related advances in targeted alpha radiotherapy.

The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy.

BACKGROUND: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new technique that enables the use of alpha particles for the treatment of solid tumors. Alpha DaRT employs interstitial sources carrying a few µ $\mu$ Ci of 224 $^{224}$ Ra below their surface, designed to release a chain of short-lived atoms (progeny of 224 $^{224}$ Ra) which emit alpha particles, along with beta, Auger, and conversion electrons, x- and gamma rays. These atoms diffuse around the source and create-primarily through their alpha decays-a lethal high-dose region measuring a few millimeters in diameter. PURPOSE: While previous studies focused on the dose from the alpha emissions alone, this work addresses the electron and photon dose contributed by the diffusing atoms and by the atoms remaining on the source surface, for both a single Alpha DaRT source and multi-source lattices. This allows to evaluate the low-LET contribution to the tumor dose and tumor cell survival, and demonstrate the sparing of surrounding healthy tissue. METHODS: The low-LET dose is calculated using the EGSnrc and FLUKA Monte Carlo (MC) codes. We compare the results of a simple line-source approximation with no diffusion to those of a full simulation, which implements a realistic source geometry and the spread of diffusing atoms. We consider two opposite scenarios: one with low diffusion and high 212 $^{212}$ Pb leakage, and the other with high diffusion and low leakage. The low-LET dose in source lattices is calculated by superposition of single-source contributions. Its effect on cell survival is estimated with the linear quadratic model in the limit of low dose rate. RESULTS: For sources carrying 3  µ $\umu$ Ci/cm 224 $^{224}$ Ra arranged in a hexagonal lattice with 4 mm spacing, the minimal low-LET dose between sources is ∼ 18 - 30 $\sim 18-30$  Gy for the two test cases and is dominated by the beta contribution. The low-LET dose drops below 5 Gy ∼ 3 $\sim 3$  mm away from the outermost source in the lattice with an effective maximal dose rate of < 0.04 $<0.04$  Gy/h. The accuracy of the line-source/no-diffusion approximation is ∼ 15 % $\sim 15\%$ for the total low-LET dose over clinically relevant distances (2-4 mm). The low-LET dose reduces tumor cell survival by a factor of ∼ 2 - 200 $\sim 2-200$ . CONCLUSIONS: The low-LET dose in Alpha DaRT can be modeled by conventional MC techniques with appropriate leakage corrections to the source activity. For 3  µ $\umu$ Ci/cm 224 $^{224}$ Ra sources, the contribution of the low-LET dose can reduce cell survival inside the tumor by up to two orders of magnitude. The low-LET dose to surrounding healthy tissue is negligible. Increasing source activities by a factor of 5 can bring the low-LET dose itself to therapeutic levels, in addition to the high-LET dose contributed by alpha particles, leading to a "self-boosted" Alpha DaRT configuration, and potentially allowing to increase the lattice spacing.

Development of local-power-free, remote α-particle detection using optical fibers.

We demonstrate the application of fluorescence optical fiber coupled to a telecom grade fiber as a sensor for alpha particles using alpha-specific ZnS(Ag) scintillation materials whose wavelength is down-shifted into a low-loss region of the telecom grade fiber transmission band. Telecom-grade fiber optics offer a solution for sensing alpha radiation in deep repositories and cask storage for radioactive materials due to the stability of SiO2 under normal environmental conditions and its relative radiation hardness at low radiation doses. Long-term nuclear waste storage facilities require sensors for the detection of leakage of radioactive materials that are maintenance-free, do not require power and can survive with no 'wear out' mechanisms for decades. By accomplishing the wavelength transformation, we maximize efficiencies in the detection of α-particles and signal transport and can detect alpha scintillation at distances on the order of >1 km with a sensor that is ~3% efficient and can be easily scaled as a sensor array. This paper describes the construction and testing of the sensor including manufacture of the controlled thickness films, verification of the wavelength shift from 450 to 620 nm and optimization of the sensitivity as a function of thickness. We also model the relative sensitivity of the film as a function of film thickness, and we demonstrate a signal-to-noise ratio of 10 at a range of greater than 1 km.

A finite element method for modeling diffusion of alpha-emitting particles in tissue.

BACKGROUND: Diffusing alpha-emitters Radiation Therapy ("DaRT") is a promising new modality for the treatment of solid tumors. Interstitial sources containing 224 Ra are inserted into the tumor, producing alpha particles via the decay of 224 Ra and its daughters. The alpha particles are able to produce a "kill region" of several mm due to the diffusion of the alpha-emitting atoms. The Diffusion-Leakage (D-L) model has been proposed to describe the movement of the alpha-emitters used in DaRT in tumor tissue. PURPOSE: To date, estimating the dose delivered under the D-L model has been accomplished with numerical solutions based on finite difference methods, namely DART1D and DART2D, as well as with asymptotic expressions for the long time limit. The aim of this work is to develop a flexible method of finite elements for solving the D-L model and to validate prior solutions of the D-L model. METHODS: We develop a two-dimensional finite element solution to the D-L model implemented using the FEniCS software library. Our approach solves the variational formulation of the D-L equations on an unstructured mesh of triangular Lagrangian elements. We calculate the local dose in the mid- and axial planes of the source and validate our results against the one- and two-dimensional solutions obtained using the previously proposed numerical scheme, DART1D and DART2D. We use our model to estimate the change in dose in the source midplane as a function of the physical parameters used in the D-L model. RESULTS: The local dose at the end of a 30 day treatment period estimated by our numerical method differs from DART1D and DART2D by less than 1% in the source midplane and less than 3% along the source axis over clinically relevant distances, with the largest discrepancies in high gradient areas where the Finite Element Method (FEM) mesh has a higher element density. We find that within current experimentally estimated ranges for D-L model parameters, the dose in the source midplane at a distance of 2 mm can vary by over a factor of 3. CONCLUSIONS: The 2D finite element model reproduces the calculated dose obtained with DART1D and DART2D under the assumptions D-L model. The variation in predicted dose within current experimental ranges for model parameters suggests the necessity of further studies to better determine their statistical distributions. Finally, the FEM model can be used to calculate dose from DaRT in a variety of realistic 2D geometries beyond the D-L model.

Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.

Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (α) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of α-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative "theranostic" platforms. Herein, the current landscape of α particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides are introduced and recent efforts towards their production for research and clinical use are described. The growing popularity of these radionuclides is explained through summarizing the biological effects of α radiation on cancer cells, which include DNA damage, activation of discrete cell death programs, and downstream immune responses. Examples of efficient α-theranostic design are described with an emphasis on strategies that lead to cellular internalization and the targeting of proteins involved in therapeutic resistance. Historical barriers to the clinical deployment of α-theranostic radiopharmaceuticals are also discussed. Recent progress towards addressing these challenges is presented along with examples of incorporating α-particle therapy in pharmaceutical platforms that can be easily converted into diagnostic counterparts.

Co-production of 155Tb and 152Tb irradiating 155Gd / 151Eu tandem target with a medium energy α-particle beam.

INTRODUCTION: Four terbium isotopes 149,152,155,161Tb emitting various types of radiation can be used for both diagnostics and therapy. 152Tb emits positrons and is ideal for PET. 155Tb is considered a promising Auger emitter and a diagnostic pair for other terbium therapeutic isotopes. Several methods for the production of 155Tb using charged particle accelerators have been proposed, but they all have significant limitations. The restricted availability of this isotope hinders its medical applications. We have proposed a new method for production of 155Tb, irradiating enriched 155Gd by alpha particles. The possibility of simultaneous production of two isotopes of terbium, 152,155Tb, was also studied for more efficient cyclotron beam use. METHODS: Irradiation of 155Gd enriched targets and 155Gd / 151Eu tandem target with alpha-particles with an energy of 54 MeV was carried out at the U-150 cyclotron at the NRC "Kurchatov Institute". The cross sections of nuclear reactions on enr-155Gd were measured by the stack foil technique, detecting the gamma-radiation of the activation products. The separation of rare earth elements was performed by extraction chromatography with the LN Resin. 155Tb was produced via 155Dy decay. RESULTS: The cross sections for the 155,156Tb and 155,157Dy production were measured by the irradiation of a gadolinium target enriched with the 155Gd isotope with alpha-particles in an energy range of 54 → 33 MeV. The yield of 155Dy on a thick target at 54 MeV was 130 MBq/µAh, which makes it possible to obtain 1 GBq of 155Tb in 11 hour-irradiation with 20 µA beam current. The possibility of simultaneous production of 152,155Tb by irradiation of 155Gd and 151Eu tandem target with medium-energy alpha-particles is implemented. Optimal irradiation energy ranges of alpha -particles as 54 → 42 MeV for 155Tb and 42 → 34 MeV for 152Tb were suggested. Product activity and radionuclidic purity were calculated.

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Initial approach to application of gamma spectroscopy to alpha particles dosimetry in BNCT.

The aim of the study is to show a method of real-time determination of the dose deposited in a tissue-like medium by α-particles emitted from the 10B(n,α)7Li reaction. The applied research method is to determine the correlation between the measured density of α-particle traces and measured in real time the 478 keV prompt-gamma rays derived from the 10B(n,α)7Li reaction. To achieve this aim, an appropriate construction of an experimental set-up is needed. The experimental set-up built for the purpose of the measurements carried out in the MARIA Reactor at the National Centre for Nuclear Research in Swierk, Poland, is presented. The main challenges related to obtaining optimal conditions for the measurement of the 478 keV gamma photons; the preliminary results of spectrometric measurements and further studies are also discussed.

Study of Nuclear Reactions in Therapy of Tumors with Proton Beams.

This paper presents an assessment of nuclear reaction yields of protons, α-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au, 11B, and 10B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible.

Marshalling the Potential of Auger Electron Radiopharmaceutical Therapy.

Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 "Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments" at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.

Development of a method of evaluating PuO2 particle diameters using an alpha-particle imaging detector.

It is very important to evaluate the diameters (activity median aerodynamic diameter) of plutonium dioxide (PuO2) particles for internal exposure dose evaluation. In this study, a method of evaluating PuO2 particle diameters using an alpha-particle imaging detector was developed. PuO2 particles with different diameters were modeled by Monte Carlo simulation, and the change in the shape of the energy spectrum for each particle diameter was evaluated. Two different patterns were modeled, namely, the case of 239PuO2 and the case of PuO2 (including isotopic composition of Pu). Multiple regression analysis was performed to determine the PuO2 particle diameter from the obtained parameters. The simulated diameters and the diameters obtained with the regression model were in good agreement. The advantage of using the alpha-particle imaging detector is to measure the alpha energy spectrum for individual particle, and this allows accurate measurement of particle diameter distribution.