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Objectives. The aim of this work is to evaluate energy deposition in the nucleus and cytoplasm in targeted alpha therapy of metastatic castration-resistant prostate cancer by modeling two cell lines, PC3 (osteolytic) and LNCaP C4-2 (osteoblastic), for actinium-225, astatine-211, and radium-223 and their progeny, using Monte Carlo simulations with the GATE/Geant4 code. Approach. We developed single cell and cell clusters models to Monte Carlo simulations, performed on the GATE platform version 9.3, with the GEANT4-DNA physics list emstandard_opt3_mixed_dna for At-211, Ac-225 and Ra-223 progenies. We considered three radionuclide distributions as a sources: the nucleus, the cytoplasm and the whole cell. Main results. When the nucleus was considered as a target, the S -values (N←N) calculated for At-211, Ac-225 and Ra-223 progenies were significantly higher, within 60%-90%, than S -values (N←Cy), demonstrating less influence of cytoplasm only internalization. When the cytoplasm was considering as a target, the S -values (Cy←Cy) calculated for At-211, Ac-225 and Ra-223 progeny were significantly higher, within 30%–90%, than the S -values (Cy←N). When no progeny migration occurs and for target nucleus, the cumulative S -values (N←N) calculated for At-211, Ac-225 and Ra-223 were significantly higher, within 50%–70%, than the S -values (N←N) computed for At-211, Ac-225, and Ra-223. Comparing the cumulative S -values, Ac-225 and Ra-223 therapies is more effective, in terms of deposited energy in a target, than that with At-211. Significance. The data presented in this research indicates that Ac-225 therapy may be the optimum choice due to the energy deposited in the nucleus, as long as the recoil effects and redistribution of progeny are understood. In contrast, At-211 is an alternative to avoid progeny migration. However, to completely analyze the efficacy of radionuclide therapy, other parameters must be considered, such as biological half-life, stability of the transport molecule, progeny migration, excretion pathways, and uptake in different organs. [ABSTRACT FROM AUTHOR]

Objective. The development of alpha-emitting radiopharmaceuticals using 225Ac (t ½ = 9.92 d) benefits from the quantitative determination of its biodistribution and is not always easy to directly measure. An element-equivalent matched-pair would allow for more accurate biodistribution and dosimetry estimates. 226Ac (t ½ = 29.4 h) is a candidate isotope for in vivo imaging of preclinical 225Ac radiopharmaceuticals, given its 158 keV and 230 keV gamma emissions making it suitable for quantitative SPECT imaging. This work aimed to conduct a performance assessment for 226Ac imaging and presents the first-ever 226Ac SPECT images. Approach. To establish imaging performance with regards to contrast and noise, image quality phantoms were scanned using a microSPECT/CT system. To assess the resolution, a hot rod phantom with cylindrical rods with diameters between 0.85 and 1.70 mm was additionally imaged. Two collimators were evaluated: a high-energy ultra-high resolution (HEUHR) collimator and an extra ultra-high sensitivity (UHS) collimator. Images were reconstructed from two distinct photopeaks at 158 keV and 230 keV. Main results. The HEUHR SPECT image measurements of high activity concentration regions were consistent with values determined independently via gamma spectroscopy, within 9% error. The lower energy 158 keV photopeak images demonstrated slightly better contrast recovery. In the resolution phantom, the UHS collimator only resolved rods ≥1.30 mm and ≥1.50 mm for the 158 keV and 230 keV photopeaks, respectively, while the HEUHR collimator clearly resolved all rods, with resolution <0.85 mm. Significance. Overall, the feasibility of preclinical imaging with 226Ac was demonstrated with quantitative SPECT imaging achieved for both its 158 keV and 230 keV photopeaks. The HEUHR collimator is recommended for imaging 226Ac activity distributions in small animals due to its resolution <0.85 mm. Future work will explore the feasibility of using 226Ac both as an element-equivalent isotope for 225Ac radiopharmaceuticals, or as a standalone therapeutic isotope. [ABSTRACT FROM AUTHOR]

Objective. For certain radionuclides that decay through emitting two or more gamma photons consecutively within a short time intervalâ€"called cascade gamma-rays, the location where a radiopharmaceutical molecule emits cascade gamma-rays can be identified through coincidence detection of the photons. If each cascade photon is detected through a collimation mechanism, the location of the molecule can be inferred from the intersection of the back-projections of the two photons. Approach. In this work, we report the design and evaluation of a three-dimensional stationary imager based on this concept for imaging distributions of cascade-emitting radionuclides in radiopharmaceutical therapy. The imager was composed of two gamma-ray cameras assembled in an L-shape. Both cameras were NaI(Tl) scintillator based, one with a multi-slit collimator, the other with a multi-pinhole collimator. The field of view (FOV) was 100 mm (âˆ...) × 100 mm (L). Based on the unique characteristics of the cascade coincidence events, we used a direct back-projection algorithm to reconstruct point source images for assessing the imager’s intrinsic spatial resolution and the standard maximum likelihood expectation maximization algorithm for reconstructing phantom images. Main results. We evaluated the performance of the imager in both simulated and prototype form with radionuclide 177Lu (cascade photon emitter). On the simulated imager, the coincidence detection efficiency at the center of FOV was 3.85 × 10âˆ'6, the spatial resolution was 7.0 mm. On the prototype imager, the corresponding values were 3.20 × 10âˆ'6 and 6.7 mm, respectively. Simulated hot-rod and experimental cardiac phantom studies demonstrate the first three-dimensional cascade gamma coincidence imager is fully functional. [ABSTRACT FROM AUTHOR]

Objective . This work introduces a novel approach to performing active and passive dosimetry for beta-emitting radionuclides in solution using common dosimeters. The measurements are compared to absorbed dose to water ( D w . A cylindrical, acrylic SPECT/CT compatible phantom capable of housing an IBA EFD diode, Exradin A20-375 parallel plate ion chamber, unlaminated EBT3 film, and thin TLD100 microcubes was constructed for the purpose of measuring absorbed dose to water from solutions of common beta-emitting radiopharmaceutical therapy agents. The phantom is equipped with removable detector inserts that allow for multiple configurations and is designed to be used for validation of image-based absorbed dose estimates with detector measurements. Two experiments with Approach . A cylindrical, acrylic SPECT/CT compatible phantom capable of housing an IBA EFD diode, Exradin A20-375 parallel plate ion chamber, unlaminated EBT3 film, and thin TLD100 microcubes was constructed for the purpose of measuring absorbed dose to water from solutions of common beta-emitting radiopharmaceutical therapy agents. The phantom is equipped with removable detector inserts that allow for multiple configurations and is designed to be used for validation of image-based absorbed dose estimates with detector measurements. Two experiments with 131 I and one experiment with 177 Lu were conducted over extended measurement intervals with starting activities of approximately 150-350 MBq. Measurement data was compared to Monte Carlo simulations using the egs&#95;chamber user code in EGSnrc 2019. Main results . Agreement within k = 1 uncertainty between measured and MC predicted D w was observed for all dosimeters, except the A20-375 ion chamber during the second 131 I experiment. Despite the agreement, the measured values were generally lower than predicted values by 5%-15%. The uncertainties at k  = 1 remain large (5%-30% depending on the dosimeter) relative to other forms of radiation therapy. Significance . Despite high uncertainties, the overall agreement between measured and simulated absorbed doses is promising for the use of dosimeter-based RPT measurements in the validation of MC predicted D w ., (Creative Commons Attribution license.)

Objective .This project aims to provide a novel method for performing dosimetry measurements on TRT radionuclides using a custom-made SPECT/CT compatible phantom, common active and passive detectors, and Monte Carlo simulations. In this work we present a feasibility study using 99m Tc for a novel approach to obtaining reproducible measurements of absorbed-dose-to-water from radionuclide solutions using active and passive detectors in a custom phantom for the purpose of benchmarking Monte Carlo-based absorbed-dose-to-water estimates. Approach . A cylindrical, acrylic SPECT/CT compatible phantom capable of housing an IBA EFD diode, SNC600c Farmer type ion chamber, and TLD-100 microcubes was designed and built for the purpose of assessing internal absorbed-dose-to-water at various points within a solution of 99m Tc. The phantom is equipped with removable inserts that allow for numerous detector configurations and is designed to be used for verification of SPECT/CT-based absorbed-dose estimates with traceable detector measurements at multiple locations. Three experiments were conducted with exposure times ranging from 11 to 21 h with starting activities of approximately 10-16 GBq. Measurement data was compared to Monte Carlo simulations using the egs&#95;chamber user code in EGSnrc 2019. Main results . In general, the ionization chamber measurements agreed with the Monte Carlo simulations within k = 1 uncertainty values (±4% and ±7%, respectively). Measurements from the TLDs yielded results within k = 1 agreement of the MC prediction (±6% and ±5%, respectively). Agreement within k = 1 uncertainty (±6% and ±7%, respectively) was obtained for the diode for one of three conducted experiments. Significance . While relatively large uncertainties remain, the agreement between measured and simulated absorbed-doses provides proof of principal that dosimetry of radionuclide solutions with active detectors may be performed using this type of phantom with potential modifications for beta-emitting radionuclides to be introduced in future work., (Creative Commons Attribution license.)