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Change of self-absorbed S-values in three organs (liver, kidneys, spleen) when scaling their masses with (a) ¹⁸F, and (b) ⁹⁰Y.
Source publication
Nuclear medicine and radiation therapy, although well established, are still rapidly evolving, by exploiting animal models, aiming to define precise dosimetry in molecular imaging protocols. The purpose of the present study was to create a dataset based on the MOBY phantom for the calculation of organ-to-organ S-values of commonly used radionuclide...
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Purpose:
Absorbed dose calculation by kernel convolution requires the prior determination of dose point kernels (DPK). This study reports on the design, implementation, and test of a multi-target regressor approach to generate the DPKs for monoenergetic sources and a model to obtain DPKs for beta emitters.
Methods:
DPK for monoenergetic electron...
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Background:
Imaging of cell death can provide an early indication of treatment response in cancer. [99mTc]Tc-Duramycin is a small-peptide SPECT tracer that recognizes both apoptotic and necrotic cells by binding to phosphatidylethanolamine present in the cell membrane. Preclinically, this tracer has shown to have favorable pharmacokinetics and sel...
PurposeIn the era of precision medicine, patient-specific dose calculation using Monte Carlo (MC) simulations is deemed the gold standard technique for risk-benefit analysis of radiation hazards and correlation with patient outcome. Hence, we propose a novel method to perform whole-body personalized organ-level dosimetry taking into account the het...
Objective:
The direct Monte Carlo (MC) simulation of radiation transport exploiting morphological and functional tomographic imaging as input data is considered the gold standard for internal dosimetry in nuclear medicine, and it is increasingly used in studies regarding Trans-Arterial Radio-Embolization (TARE). However, artefacts affecting the fu...
The purpose of this work was to validate GATE-based clinical scale absorbed dose calculations in nuclear medicine dosimetry.
GATE (version 6.2) and MCNPX (version 2.7.a) were used to derive dosimetric parameters (absorbed fractions, specific absorbed fractions and S-values) for the reference female computational model proposed by the International...
Citations
... The rat liver mass was 12-15 g, the S value (Activity Radiation exposure conversion coefficient) of 177 Lu in liver was 11.2 by digimouse voxel phantom [45]. Consequently, the absorbed dose for 37 MBq of 177 Lu was calculated as 32-41 Gy, which is comparable to the recommended dose from European Association of Nuclear Medicine (EANM) 90 Y-microsphere therapy guideline. ...
Background
Transarterial radioembolization (TARE) with ⁹⁰ Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load ¹⁷⁷ Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of ¹⁷⁷ Lu-PDA-CS-MgO microspheres for HCC treatment.
Methods
Chitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The ¹⁷⁷ Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of ¹⁷⁷ Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres.
Results
The composite ¹⁷⁷ Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that ¹⁷⁷ Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with ¹⁷⁷ Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that ¹⁷⁷ Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of ¹⁷⁷ Lu-PDA-CS-MgO microspheres in vivo.
Conclusion
Our study demonstrated that ¹⁷⁷ Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy.
Graphical Abstract
Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.
... The summation over source organs in Eq. (1) can be simplified to just one term for 58m Co because the source organ entirely absorbs the radiation (24.95 keV/decay). The radiation dose to female humans was calculated by scaling the radiation dose to mice with organ mass ratios [26][27][28]. The absorbed dose rate per unit activity for 58g Co was obtained from OpenDose [29]. ...
... Average organ masses and absorbed dose rate per unit activity can be found in supplemental Table 1. Mouse organ masses were taken from Table 3 of [28]. Applying mass-scaled human-derived absorbed dose rate per unit activity should overestimate absorbed dose to off-target organs from 58g Co in mice because contributions from high energy photons are typically more significant in humans than mice. ...
Unlabelled:
Neurotensin receptor 1 (NTSR1) can stimulate tumor proliferation through neurotensin (NTS) activation and are overexpressed by a variety of cancers. The high binding affinity of NTS/NTSR1 makes radiolabeled NTS derivatives interesting for cancer diagnosis and staging. Internalization of NTS/NTSR1 also suggests therapeutic application with high LET alpha particles and low energy electrons. We investigated the therapeutic efficacy of [58mCo]Co-NOTA-NT-20.3 in vivo using murine models xenografted with NTSR1-positive HT29 human colorectal adenocarcinoma cells, and utilized [55Co]Co-NOTA-NT-20.3 for dosimetry.
Methods:
Targeting properties and cytotoxicity of [55/58mCo]Co-NOTA-NT-20.3 were assessed with HT29 cells. Female nude mice were xenografted with HT29 tumors and administered [55Co or 58mCo]Co-NOTA-NT-20.3 to evaluate pharmacokinetics or for therapy, respectively. Dosimetry calculations followed the Medical Internal Radiation Dose (MIRD) formalism and human absorbed dose rate per unit activity were obtained from OpenDose. The pilot therapy study consisted of two groups (each N = 3) receiving 110 ± 15 MBq and 26 ± 6 MBq [58mCo]Co-NOTA-NT-20.3 one week after tumor inoculation, and control (N = 3). Tumor sizes and masses were measured twice a week after therapy. Complete blood count and kidney histology were also performed to assess toxicity.
Results:
HPLC measured radiochemical purity of [55,58mCo]Co-NOTA-NT-20.3 > 99 %. Labeled compounds retained NTS targeting properties. [58mCo]Co-NOTA-NT-20.3 exhibited cytotoxicity for HT29 cells and was >15× more potent than [58mCo]CoCl2. Xenografted tumors responded modestly to administered doses, but mice showed no signs of radiotoxicity. Absorbed dose to tumor and kidney with 110 MBq [58mCo]Co-NOTA-NT-20.3 were 0.6 Gy and 0.8 Gy, respectively, and other organs received less than half of the absorbed dose to tumor. Off-target radiation dose from cobalt-58g was small but reduces the therapeutic window.
Conclusion:
The enhanced in vitro cytotoxicity and high tumor-to-background led us to investigate the therapeutic efficacy of [58mCo]Co-NOTA-NT-20.3 in vivo. Although we were unable to induce tumor response commensurate with [177Lu]Lu-NT127 (NLys-Lys-Pro-Tyr-Tle-Leu) studies involving similar time-integrated activity, the absence of observed toxicity may constitute an opportunity for targeting vectors with improved uptake and/or retention to avoid the aftereffects of other high-LET radioactive emissions. Future studies with higher uptake, activity and/or multiple dosing regimens are warranted. The theranostic approach employed in this work was crucial for dosimetry analysis.
... At the end of the treatment, bladders were washed 3 times with PBS, and catheters were removed. Dosimetry assessment of the bladder wall was estimated utilizing the previously published results of MOBY phantom model calculation of S-value with GATE MC toolkit[19]. ...
PurposeBladder cancer represents 3% of all new cancer diagnoses per year. We propose intravesical radionuclide therapy using the β-emitter 90Y linked to DOTA-biotin-avidin ([90Y]DBA) to deliver short-range radiation against non-muscle invasive bladder cancer (NMIBC).Material and methodsImage-guided biodistribution of intravesical DBA was investigated in an animal model by radiolabeling DBA with the 68Ga and dynamic microPET imaging following intravesical infusion of [68Ga]DBA for up to 4 h and post-necropsy γ-counting of organs. The antitumor activity of [90Y]DBA was investigated using an orthotopic MB49 murine bladder cancer model. Mice were injected with luciferase-expressing MB49 cells and treated via intravesical administration with 9.2 MBq of [90Y]DBA or unlabeled DBA 3 days after the tumor implantation. Bioluminescence imaging was conducted after tumor implantation to monitor the bladder tumor growth. In addition, we investigated the effects of [90Y]DBA radiation on urothelial histology with immunohistochemistry analysis of bladder morphology.ResultsOur results demonstrated that DBA is contained in the bladder for up to 4 h after intravesical infusion. A single dose of [90Y]DBA radiation treatment significantly reduced growth of MB49 bladder carcinoma. Attaching 90Y-DOTA-biotin to avidin prevents its re-absorption into the blood and distribution throughout the rest of the body. Furthermore, immunohistochemistry demonstrated that [90Y]DBA radiation treatment did not cause short-term damage to urothelium at day 10, which appeared similar to the normal urothelium of healthy mice.Conclusion
Our data demonstrates the potential of intravesical [90Y]DBA as a treatment for non-muscle invasive bladder cancer.
... However, this is the common practice in mouse simulations. (Kinase et al., 2008;Sinha, 2018;Bitar et al., 2007;Kostou et al., 2016;Hindorf et al., 2004;Boutaleb et al., 2009;Stabin, 2019). Also, special attention should be given to the hollow organs (heart, bladder, stomach) for which the S-values are determined for the organs alone, as is practice in these calculations (Kinase et al., 2008). ...
... Calculations of S-values in DIGIMOUSE and other mouse models for 99m Tc and other radionuclides haven been performed (Sinha, 2018;Bitar et al., 2007;Kostou et al., 2016;Hindorf et al., 2004;Boutaleb et al., 2009;Stabin, 2019). Some results are published for calculations of S-values in other phantoms. ...
... In the case of Bitar et al. (2007) a female mouse of 30 g mass was used. In the case of Kostou et al. (2016) they used a mouse of mass 34 g, whereas Boutaleb et al. (2009) used different models, including DIGIMOUSE. ...
A correct dosimetry of radionuclides in small animals is of great importance for the development of radiopharmaceuticals.
The objective of this study was to determine the S-values for 99mTc in the DIGIMOUSE voxel phantom, using the MIRD methodology and Monte Carlo simulations.
For benchmarking, self-absorbed fractions in the kidneys were determined, for photons and electrons, using a monoenergetic source in the energy range 10 keV to 4 MeV. Obtained results showed a deviation of 5% or less for photons and for electrons up to 1 MeV when compared to results to other studies found in the literature.
After validation, a source of 99mTc was defined in various source organs to determine the S-values.
After this, the self-absorption S-values were fitted as a function of the inverse of the mass yielding extremely accurate results. It can be shown that the electronic S-values follow a 1/m function with a multiplication constant of 12.9 keV which corresponds to the average energy of the emitted electrons of 13.9 keV.
Furthermore, a qualitative analysis of the crossfire S-values is provided. The main affected organs by crossfire radiation are the stomach, the spleen, and the pancreas, whereas the heart and the lungs are mainly affected by each other, respectively.
The results obtained for the S-values were also compared with previously published results. The differences obtained between the different studies can be justified by differences in the choice of density and stoichiometric composition of the organs of DIGIMOUSE relative to other mouse voxel phantoms.
Finally, the obtained results can be useful for researchers who need to perform dosimetric calculations of novel radiopharmaceuticals labelled with 99mTc.
... However, this is the common practice in mouse simulations. (Kinase et al., 2008;Sinha, 2018;Bitar et al., 2007;Kostou et al., 2016;Hindorf et al., 2004;Boutaleb et al., 2009;Stabin, 2019). Also, special attention should be given to the hollow organs (heart, bladder, stomach) for which the S-values are determined for the organs alone, as is practice in these calculations (Kinase et al., 2008). ...
... Calculations of S-values in DIGIMOUSE and other mouse models for 99m Tc and other radionuclides haven been performed (Sinha, 2018;Bitar et al., 2007;Kostou et al., 2016;Hindorf et al., 2004;Boutaleb et al., 2009;Stabin, 2019). Some results are published for calculations of S-values in other phantoms. ...
... In the case of Bitar et al. (2007) a female mouse of 30 g mass was used. In the case of Kostou et al. (2016) they used a mouse of mass 34 g, whereas Boutaleb et al. (2009) used different models, including DIGIMOUSE. ...
... Puede también darse el caso en que los simuladores se usen para la investigación y desarrollo: en 2015 se aplicó un simulador de tomografías para diseñar un algoritmo que optimice los parámetros de reconstrucción iterativa y guíe protocolos de reducción de dosis en experimentos físicos [346]; y en 2016 se aplicó el simulador físico GATE, con un toolkit de simulación Monte-Carlo, para la medición de valores S (S-values) órgano a órgano de los radionúclidos de uso común en ratones [347]. En esta parte también puede mencionarse el estudio anteriormente citado sobre los efectos del sonido en el desempeño de los doctores en emergencias [332], y la investigación de 2017 que buscó evaluar el uso de modelos secos como simuladores adecuados para practicar la reparación artroscópica del manguito rotador y reparación del labrum [316]. ...
Un panorama de simuladores médicos para educación Los profesionales en el área encontrarán ejemplos sobre lo que se puede usar en la formación de estudiantes antes de entrar en contacto con pacientes reales
... This change in volume was taken into account when calculating activities in the tumor. [32,33], except for: a mass from [34], and b same blood fraction as for the humans, taken from [30]. ...
Pharmacokinetic modeling of the radiopharmaceuticals used in molecular radiotherapy is an important step towards accurate radiation dosimetry of such therapies. In this paper, we present a pharmacokinetic model for CLR1404, a phospholipid ether analog that, labeled with 124I/131I, has emerged as a promising theranostic agent. We follow a systematic approach for the model construction based on a decoupling process applied to previously published experimental data, and using the goodness-of-fit, Sobol’s sensitivity analysis, and the Akaike Information Criterion to construct the optimal form of the model, investigate potential simplifications, and study factor prioritization. This methodology was applied to previously published experimental human time-activity curves for 9 organs. The resulting model consists of 17 compartments involved in the CLR1404 metabolism. Activity dynamics in most tissues are well described by a blood contribution plus a two-compartment system, describing fast and slow uptakes. The model can fit both clinical and pre-clinical kinetic data of 124I/131I. In addition, we have investigated how simple fits (exponential and biexponential) differ from the complete model. Such fits, despite providing a less accurate description of time-activity curves, may be a viable alternative when limited data is available in a practical case.
... In the scaling of S-values for organ masses, the self-organ S-values have an absolute correlation, however the effect and the variations in the cross organ S-values are not clear, because it is necessary to consider the entire anatomy of the mouse (Kostou et al., 2016). For a more accurate radiation dosimetry study it is important to take into account the characteristics of the available animals, as several mouse strains can be used in preclinical research. ...
... Single Photon Emis sion Tomography (SPECT) imaging (Ljungberg et al., 2013) (Sarrut et al., 2014) (Papadimitroulas, 2017). Monte Carlo simulations combined with computational models offer significant tools for absorbed dose calculation and an accurate anatomic description of relevant species (Kostou et al., 2016). Many computational animal models have been reported in the literature (Xie and Zaidi, 2016). ...
... Zhang et al., 2009 developed a 28 g voxel-based mouse from cryosection image data (); and Bitar et al., 2007 created a model from a female nude mouse (30g) (). Other models were developed from MOBY by Keenan et al., 2010 andKostou et al., 2016 generating three mouse models with different masses, 22, 28 and 34 g, to investigate the impact of rescaled organ masses using the MOBY phantom in preclinical simulations with GATE. ...
The aims of this study were to construct a mouse model based on experimental data and to evaluate two approaches for a radiation dosimetry study on the development of a new radiopharmaceutical based on MIRD Formalism with free software. The first one obtaining S-values from a reference model and with these data calculating the absorbed doses. The second consisting of a specific anatomy mouse considering characteristics such as strain, gender, age, and weight used in preclinical studies comparing the results obtained for the new radiopharmaceutical 99mTc-Ixolaris. A voxelized mouse model (C57BL/6 lineage) based on Computed Tomography images with ten segmented organs was developed by 3D SLICER software and was used as input in GATE Monte Carlo simulations (version 7.1) to determine organ absorbed dose distribution by the proposed approaches. The first method consisted of obtaining the S-values for each source organ by performing separate simulations, and the second method obtained the absorbed dose in each target organ through a single simulation containing all source organs (real radiopharmaceutical biodistributions). Absorbed dose distribution volumetric maps were obtained for each simulation. Using the first method, the numerical data were extracted from volumetric maps to determine the S-values for each source organ and in the second method the absorbed dose was obtained directly from simulation, without S-value tables. The preclinical dosimetry evaluation showed good agreement between both methods but each one has its own advantages and disadvantages: the first has less statistical uncertainties than the second method and the S-values obtained for a standard model can be scaled to other mouse sizes; the second method requires shorter simulation computational time, considering a specific anatomy mouse, using a real biodistribution with all source organs in the simulation without construction of S-value tables.
... Our prospective studies include the complete power dissipation mapping of efficient magnetic fluids throughout a wide range of concentrations. In addition, the development of numerical models aimed for simulations of biological systems, combining mapped magnetic fluids with computational phantoms such as XCAT or MOBY [72][73][74][75][76][77]. Such models could be exploited to improve thermal dose delivery by optimizing the MNPs' distribution within the ROI. ...
Purpose:
The purpose of this study is to employ magnetic fluid hyperthermia simulations in the precise computation of Specific Absorption Rate functions -SAR(T)-, and in the evaluation of the predictive capacity of different SAR calculation methods.
Methods:
Magnetic fluid hyperthermia experiments were carried out using magnetite-based nanofluids. The respective SAR values were estimated through four different calculation methods including the initial slope method, the Box-Lucas method, the corrected slope method and the incremental analysis method (INCAM). A novel numerical model combining the heat transfer equations and the Navier-Stokes equations was developed to reproduce the experimental heating process. To address variations in heating efficiency with temperature, the expression of the power dissipation as a Gaussian function of temperature was introduced and the Levenberg-Marquardt optimization algorithm was employed to compute the function parameters and determine the function's effective branch within each measurement's temperature range. The power dissipation function was then reduced to the respective SAR function.
Results:
The INCAM exhibited the lowest relative errors ranging between 0.62 and 15.03% with respect to the simulations. SAR(T) functions exhibited significant variations, up to 45%, within the MFH-relevant temperature range.
Conclusions:
The examined calculation methods are not suitable to accurately quantify the heating efficiency of a magnetic fluid. Numerical models can be exploited to effectively compute SAR(T) and contribute to the development of robust hyperthermia treatment planning applications.
... The MOBY phantom has been implemented by several investigators for mouse dosimetry calculations (25)(26)(27). Using methodology described in the Supplemental Information, MOBY was converted to tetrahedral geometry to enable its use within PARaDIM; 18 F self S-values for MOBY's constituent organs were calculated and compared with previous literature which utilized voxelbased methods with this phantom. ...
Mesh-type and voxel-based computational phantoms comprise the current state-of-the-art for internal dose assessment via Monte Carlo simulations, but excel in different aspects, with mesh type phantoms offering advantages over their voxel counterparts in terms of their flexibility and realistic representation of detailed patient- or subject-specific anatomy. We have developed PARaDIM, a freeware application for implementing tetrahedral mesh-type phantoms in absorbed dose calculations via the Particle and Heavy Ion Transport code System (PHITS). It considers all medically relevant radionuclides including alpha, beta, gamma, positron, and Auger/conversion electron emitters, and handles calculation of mean dose to individual regions, as well as 3D dose distributions for visualization and analysis in a variety of medical imaging softwares. This work describes the development of PARaDIM, documents the measures taken to test and validate its performance, and presents examples to illustrate its uses. Methods: Human, small animal, and cell-level dose calculations were performed with PARaDIM and the results compared with those of widely accepted dosimetry programs and literature data. Several tetrahedral phantoms were developed or adapted using computer-aided modeling techniques for these comparisons. Results: For human dose calculations, agreement of PARaDIM with OLINDA 2.0 was good – within 10-20% for most organs – despite geometric differences among the phantoms tested. Agreement with MIRDcell for cell-level S-value calculations was within 5% in most cases. Conclusion: PARaDIM extends the use of Monte Carlo dose calculations to the broader community in nuclear medicine by providing a user-friendly graphical user interface for calculation setup and execution. PARaDIM leverages the enhanced anatomical realism provided by advanced computational reference phantoms or bespoke image-derived phantoms to enable improved assessments of radiation doses in a variety of radiopharmaceutical use cases, research, and preclinical development.
PARaDIM is available at: www.paradim-dose.org
