Active and passive dosimetry for beta-emitting radiopharmaceutical therapy agents in a custom SPECT/CT compatible phantom.

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 (Dw) estimates from Monte Carlo (MC) simulations. We present a method for obtaining absorbed dose to water, measured with dosimeters, from beta-emitting radiopharmaceutical agents using a custom SPECT/CT compatible phantom for validation of Monte Carlo based absorbed dose to water estimates.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 with131I and one experiment with177Lu 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_chamber user code in EGSnrc 2019.Main results. Agreement withink= 1 uncertainty between measured and MC predictedDwwas observed for all dosimeters, except the A20-375 ion chamber during the second131I experiment. Despite the agreement, the measured values were generally lower than predicted values by 5%-15%. The uncertainties atk = 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 predictedDw.

Linear Boltzmann equation solver for voxel-level dosimetry in radiopharmaceutical therapy: Comparison with Monte Carlo and kernel convolution.

BACKGROUND: With recent interest in patient-specific dosimetry for radiopharmaceutical therapy (RPT) and selective internal radiation therapy (SIRT), an increasing number of voxel-based algorithms are being evaluated. Monte Carlo (MC) radiation transport, generally considered to be the most accurate among different methods for voxel-level absorbed dose estimation, can be computationally inefficient for routine clinical use. PURPOSE: This work demonstrates a recently implemented grid-based linear Boltzmann transport equation (LBTE) solver for fast and accurate voxel-based dosimetry in RPT and SIRT and benchmarks it against MC. METHODS: A deterministic LBTE solver (Acuros MRT) was implemented within a commercial RPT dosimetry package (Velocity 4.1). The LBTE is directly discretized using an adaptive mesh refined grid and then the coupled photon-electron radiation transport is iteratively solved inside specified volumes to estimate radiation doses from both photons and charged particles in heterogeneous media. To evaluate the performance of the LBTE solver for RPT and SIRT applications, 177Lu SPECT/CT, 90Y PET/CT, and 131I SPECT/CT images of phantoms and patients were used. Multiple lesions (2-1052 mL) and normal organs were delineated for each study. Voxel dosimetry was performed with the LBTE solver, dose voxel kernel (DVK) convolution with density correction, and a validated in-house MC code using the same time-integrated activity and density maps as input to the different dose engines. The resulting dose maps, difference maps, and dose-volume-histogram (DVH) metrics were compared, to assess the voxel-level agreement. Evaluation of mean absorbed dose included comparison with structure-level estimates from OLINDA. RESULTS: In the phantom inserts/compartments, the LBTE solver versus MC and DVK convolution demonstrated good agreement with mean absorbed dose and DVH metrics agreeing to within 5% except for the D90 and D70 metrics of a very low activity concentration insert of 90Y where the agreement was within 15%. In the patient studies (five patients imaged after 177Lu DOTATATE RPT, five after 90Y SIRT, and two after 131I radioimmunotherapy), in general, there was better agreement between the LBTE solver and MC than between LBTE solver and DVK convolution for mean absorbed dose and voxel-level evaluations. Across all patients for all three radionuclides, for soft tissue structures (kidney, liver, lesions), the mean absorbed dose estimates from the LBTE solver were in good agreement with those from MC (median difference < 1%, maximum 9%) and those from DVK (median difference < 5%, maximum 9%). The LBTE and OLINDA estimates for mean absorbed dose in kidneys and liver agreed to within 10%, but differences for lesions were larger with a maximum 14% for 177Lu, 23% for 90Y, and 26% for 131I. For bone regions, the agreement in mean absorbed doses between LBTE and both MC and DVK were similar (median < 11%, max 11%) while for lung the agreement between LBTE and MC (median < 1%, max 8%) was substantially better than between LBTE and DVK (median < 16%, max 33%). Voxel level estimates for soft tissue structures also showed good agreement between the LBTE solver and both MC and DVK with a median difference < 5% (maximum < 13%) for the DVH metrics with all three radionuclides. The largest difference in DVH metrics was for the D90 and D70 metric in lung and bone where the uptake was low. Here, the difference between LBTE and MC had a median value < 14% (maximum 23%) for bone and < 4% (maximum 37%) for lung, while the corresponding differences between LBTE and DVK were < 23% (maximum 31%) and < 67% (maximum 313%), respectively. For a typical patient with a matrix size of 166 × 166 × 129 (voxel size 3 × 3 × 3 mm3), voxel dosimetry using the LBTE solver was as fast as ∼2 min on a desktop computer. CONCLUSION: Having established good agreement between the LBTE solver and MC for RPT and SIRT applications, the LBTE solver is a viable option for voxel dosimetry that can be faster than MC. Further analysis is being performed to encompass the broad range of radionuclides and conditions encountered clinically.

SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE.

Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo-derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors. Methods: Twenty patients each receiving 4 treatment cycles of [177Lu]Lu-DOTATATE were included. Multiple-time-point 177Lu SPECT/CT imaging-based RM dosimetry was performed using an artificial intelligence-driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles. Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D median,vertebrae) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6-2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D median,vertebrae (r = -0.64, P = 0.015), D median,lumbar (r = -0.72, P = 0.0038), D median,thoracic (r = -0.58, P = 0.029), and D average,vertebrae (r = -0.66, P = 0.010), where D median,lumbar and D median,thoracic are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D average,vertebrae is the mass-weighted average absorbed dose of all vertebrae. Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

Low cost, high temporal resolution optical fiber-based γ-photon sensor for real-time pre-clinical evaluation of cancer-targeting radiopharmaceuticals.

Cancer radiopharmaceutical therapies (RPTs) have demonstrated great promise in the treatment of neuroendocrine and prostate cancer, giving hope to late-stage metastatic cancer patients with currently very few treatment options. These therapies have sparked a large amount of interest in pre-clinical research due to their ability to target metastatic disease, with many research efforts focused towards developing and evaluating targeted RPTs for different cancer types in in vivo models. Here we describe a method for monitoring real-time in vivo binding kinetics for the pre-clinical evaluation of cancer RPTs. Recognizing the significant heterogeneity in biodistribution of RPTs among even genetically identical animal models, this approach offers long-term monitoring of the same in vivo organism without euthanasia in contrast to ex vivo tissue dosimetry, while providing high temporal resolution with a low-cost, easily assembled platform, that is not present in small-animal SPECT/CTs. The method utilizes the developed optical fiber-based γ-photon biosensor, characterized to have a wide linear dynamic range with Lutetium-177 (177Lu) activity (0.5-500 µCi/mL), a common radioisotope used in cancer RPT. The probe's ability to track in vivo uptake relative to SPECT/CT and ex vivo dosimetry techniques was verified by administering 177Lu-PSMA-617 to mouse models bearing human prostate cancer tumors (PC3-PIP, PC3-flu). With this method for monitoring RPT uptake, it is possible to evaluate changes in tissue uptake at temporal resolutions <1 min to determine RPT biodistribution in pre-clinical models and better understand dose relationships with tumor ablation, toxicity, and recurrence when attempting to move therapies towards clinical trial validation.

Tumor Control Probability and Small-Scale Monte Carlo Dosimetry: Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy.

In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for 225Ac, 177Lu, and 90Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for 225Ac, 177Lu, and 90Y was found to be 18.3 kBq (range, 18-22 kBq), 24.3 MBq (range, 20-29 MBq), and 5.6 MBq (range, 5-6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.

Assessment of cross-dose contributions from tumors within computational phantoms using a Geant4 radiation dosimetry tool exploiting hybrid analytical/voxelised geometries.

BACKGROUND: Dosimetry software tools developed for Radiopharmaceutical Therapy, such as OLINDA/EXM or IDAC-Dose, account only for radiation dose to organs from radiopharmaceutical taken up in other organs. PURPOSE: The aim of this study is to present a methodology, that can be applied to any voxelised computational model, able to account for cross-dose to organs from tumors of any shape and number enclosed within an organ. METHODS: A Geant4 application using hybrid analytical/voxelised geometries has been developed as an extension to the ICRP110_HumanPhantom Geant4 advanced example and validated against ICRP publication 133. In this new Geant4 application, tumors are defined using the Geant4 Parallel Geometry functionality, which allows the co-existence of two independent geometries in the same Monte Carlo simulation. The methodology was validated by estimating total dose to healthy tissue from 90 Y and from 177 Lu distributed within tumors of various sizes localized within the liver of the ICRP110 adult male phantom. RESULTS: Agreement of the Geant4 application with ICRP133 was within 5% when masses were adjusted for blood content. Total dose to healthy liver and to tumors was found to agree within 1% when compared to the ground truth. CONCLUSIONS: The methodology presented in this work can be extended to investigate total dose to healthy tissue from systemic uptake of radiopharmaceuticals in tumors of different sizes using any voxelised computational dosimetric model.

Development of a stand-alone precalculated Monte Carlo code to calculate the dose by alpha and beta emitters from the Ra-224 decay chain.

BACKGROUND: Recent developments in alpha and beta emitting radionuclide therapy highlight the importance of developing efficient methods for patient-specific dosimetry. Traditional tabulated methods such as Medical Internal Radiation Dose (MIRD) estimate the dose at the organ level while more recent numerical methods based on Monte Carlo (MC) simulations are able to calculate dose at the voxel level. A precalculated MC (PMC) approach was developed in this work as an alternative to time-consuming fully simulated MC. Once the spatial distribution of alpha and beta emitters is determined using imaging and/or numerical methods, the PMC code can be used to achieve an accurate voxelized 3D distribution of the deposited energy without relying on full MC calculations. PURPOSE: To implement the PMC method to calculate energy deposited by alpha and beta particles emitted from the Ra-224 decay chain. METHODS: The GEANT4 (version 10.7) MC toolkit was used to generate databases of precalculated tracks to be integrated in the PMC code as well as to benchmark its output. In this regard, energy spectra of alpha and beta particles emitted by the Ra-224 decay chain were generated using GAMOS (version 6.2.0) and imported into GEANT4 macro files. Either alpha or beta emitting sources were defined at the center of a homogeneous phantom filled with various materials such as soft tissue, bone, and lung where particles were emitted either mono-directionally (for database generation) or isotropically (for benchmarking). Two heterogeneous phantoms were used to demonstrate PMC code compatibility with boundary crossing events. Each precalculated database was generated step-by-step by storing particle track information from GEANT4 simulations followed by its integration in a PMC code developed in MATLAB. For a user-defined number of histories, one of the tracks in a given database was selected randomly and rotated randomly to reflect an isotropic emission. Afterward, deposited energy was divided between voxels based on step length in each voxel using a ray-tracing approach. The radial distribution of deposited energy was benchmarked against fully simulated MC calculations using GEANT4. The effect of the GEANT4 parameter StepMax on the accuracy and speed of the code was also investigated. RESULTS: In the case of alpha decay, primary alpha particles show the highest contribution (>99%) in deposited energy compared to their secondary particles. In most cases, protons act as the main secondary particles in the deposition of energy. However, for a lung phantom, using a range cutoff parameter of 10 µm on primary alpha particles yields a higher contribution of secondary electrons than protons. Differences between deposited energy calculated by PMC and fully simulated MC are within 2% for all alpha and beta emitters in homogeneous and heterogeneous phantoms. Additionally, statistical uncertainties are less than 1% for voxels with doses higher than 5% of the maximum dose. Moreover, optimization of the parameter StepMax is necessary to achieve the best tradeoff between code accuracy and speed. CONCLUSIONS: The PMC code shows good performance for dose calculations deposited by alpha and beta emitters. As a stand-alone algorithm, it is suitable to be integrated into clinical treatment planning systems.

Validation of Monte Carlo simulated absorbed-dose-to-water inside a custom SPECT/CT phantom using active and passive dosimeters: a feasibility study using99mTc.

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 using99mTc 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 of99mTc. 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_chamber user code in EGSnrc 2019.Main results. In general, the ionization chamber measurements agreed with the Monte Carlo simulations withink= 1 uncertainty values (±4% and ±7%, respectively). Measurements from the TLDs yielded results withink= 1 agreement of the MC prediction (±6% and ±5%, respectively). Agreement withink= 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.

Large-scale in vitro microdosimetry via live cell microscopy imaging: implications for radiosensitivity and RBE evaluations in alpha-emitter radiopharmaceutical therapy.

BACKGROUND: Alpha-emitter radiopharmaceutical therapy (αRPT) has shown promising outcomes in metastatic disease. However, the short range of the alpha particles necessitates dosimetry on a near-cellular spatial scale. Current knowledge on cellular dosimetry is primarily based on in vitro experiments using cell monolayers. The goal of such experiments is to establish cell sensitivity to absorbed dose (AD). However, AD cannot be measured directly and needs to be modeled. Current models, often idealize cells as spheroids in a regular grid (geometric model), simplify binding kinetics and ignore the stochastic nature of radioactive decay. It is unclear what the impact of such simplifications is, but oversimplification results in inaccurate and non-generalizable results, which hampers the rigorous study of the underlying radiobiology. METHODS: We systematically mapped out 3D cell geometries, clustering behavior, agent binding, internalization, and subcellular trafficking kinetics for a large cohort of live cells under representative experimental conditions using confocal microscopy. This allowed for realistic Monte Carlo-based (micro)dosimetry. Experimentally established surviving fractions of the HER2 + breast cancer cell line treated with a 212Pb-labelled anti-HER2 conjugate or external beam radiotherapy, anchored a rigorous statistical approach to cell sensitivity and relative biological effectiveness (RBE) estimation. All outcomes were compared to a reference geometric model, which allowed us to determine which aspects are crucial model components for the proper study of the underlying radiobiology. RESULTS: In total, 567 cells were measured up to 26 h post-incubation. Realistic cell clustering had a large (2x), and cell geometry a small (16.4% difference) impact on AD, compared to the geometric model. Microdosimetry revealed that more than half of the cells do not receive any dose for most of the tested conditions, greatly impacting cell sensitivity estimates. Including these stochastic effects in the model, resulted in significantly more accurate predictions of surviving fraction and RBE (permutation test; p < .01). CONCLUSIONS: This comprehensive integration of the biological and physical aspects resulted in a more accurate method of cell survival modelling in αRPT experiments. Specifically, including realistic stochastic radiation effects and cell clustering behavior is crucial to obtaining generalizable radiobiological parameters.

Experimental validation of Monte Carlo dosimetry for therapeutic beta emitters with radiochromic film in a 3D-printed phantom.

PURPOSE: Validation of dosimetry software, such as Monte Carlo (MC) radiation transport codes used for patient-specific absorbed dose estimation, is critical prior to their use in clinical decision making. However, direct experimental validation in the clinic is generally not performed for low/medium-energy beta emitters used in radiopharmaceutical therapy (RPT) due to the challenges of measuring energy deposited by short-range particles. Our objective was to design a practical phantom geometry for radiochromic film (RF)-based absorbed dose measurements of beta-emitting radionuclides and perform experiments to directly validate our in-house developed Dose Planning Method (DPM) MC code dedicated to internal dosimetry. METHODS: The experimental setup was designed for measuring absorbed dose from beta emitters that have a range sufficiently penetrating to ∼200 µm in water as well as to capture any photon contributions to absorbed dose. Assayed 177 Lu and 90 Y liquid sources, 13-450 MBq estimated to deliver 0.5-10 Gy to the sensitive layer of the RF, were injected into the cavity of two 3D-printed half-cylinders that had been sealed with 12.7 µm or 25.4 µm thick Kapton Tape. A 3.8 × 6 cm strip of GafChromic EBT3 RF was sandwiched between the two taped half-cylinders. After 2-48 h exposures, films were retrieved and wipe tested for contamination. Absorbed dose to the RF was measured using a commercial triple-channel dosimetry optimization method and a calibration generated via 6 MV photon beam. Profiles were analyzed across the central 1 cm2 area of the RF for validation. Eleven experiments were completed with 177 Lu and nine with 90 Y both in saline and a bone equivalent solution. Depth dose curves were generated for 177 Lu and 90 Y stacking multiple RF strips between a single filled half-cylinder and an acrylic backing. All experiments were modeled in DPM to generate voxelized MC absorbed dose estimates. We extended our study to benchmark general purpose MC codes MCNP6 and EGSnrc against the experimental results as well. RESULTS: A total of 20 experiments showed that both the 3D-printed phantoms and the final absorbed dose values were reproducible. The agreement between the absorbed dose estimates from the RF measurements and DPM was on average -4.0% (range -10.9% to 3.2%) for all single film 177 Lu experiments and was on average -1.0% (range -2.7% to 0.7%) for all single film 90 Y experiments. Absorbed depth dose estimates by DPM agreed with RF on average 1.2% (range -8.0% to 15.2%) across all depths for 177 Lu and on average 4.0% (range -5.0% to 9.3%) across all depths for 90 Y. DPM absorbed dose estimates agreed with estimates from EGSnrc and MCNP across the board, within 4.7% and within 3.4% for 177 Lu and 90 Y respectively, for all geometries and across all depths. MC showed that absorbed dose to RF from betas was greater than 92% of the total (betas + other radiations) for 177 Lu, indicating measurement of dominant beta contribution with our design. CONCLUSIONS: The reproducible results with a RF insert in a simple phantom designed for liquid sources demonstrate that this is a reliable setup for experimentally validating dosimetry algorithms used in therapies with beta-emitting unsealed sources. Absorbed doses estimated with the DPM MC code showed close agreement with RF measurement and with results from two general purpose MC codes, thereby validating the use of this algorithms for clinical RPT dosimetry.

Validation of Monte Carlo 131 I radiopharmaceutical dosimetry workflow using a 3D-printed anthropomorphic head and neck phantom.

PURPOSE: Approximately 50% of head and neck cancer (HNC) patients will experience loco-regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may be associated with a significant risk of irreversible damage to normal tissues. Radiopharmaceutical therapy (RPT) is a potential method to treat recurrent HNC in conjunction with EBRT. Phantoms are used to calibrate and add quantification to nuclear medicine images, and anthropomorphic phantoms can account for both the geometrical and material composition of the head and neck. In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom, and its characterization for the validation of a Monte Carlo, SPECT image-based, 131 I RPT dosimetry workflow. METHODS: 3D-printing techniques were used to create the anthropomorphic phantom from a patient CT dataset. Three 131 I SPECT/CT imaging studies were performed using a homogeneous, Jaszczak, and an anthropomorphic phantom to quantify the SPECT images using a GE Optima NM/CT 640 with a high energy general purpose collimator. The impact of collimator detector response (CDR) modeling and volume-based partial volume corrections (PVCs) upon the absorbed dose was calculated using an image-based, Geant4 Monte Carlo RPT dosimetry workflow and compared against a ground truth scenario. Finally, uncertainties were quantified in accordance with recent EANM guidelines. RESULTS: The 3D-printed anthropomorphic phantom was an accurate re-creation of patient anatomy including bone. The extrapolated Jaszczak recovery coefficients were greater than that of the 3D-printed insert (∼22.8 ml) for both the CDR and non-CDR cases (with CDR: 0.536 vs. 0.493, non-CDR: 0.445 vs. 0.426, respectively). Utilizing Jaszczak phantom PVCs, the absorbed dose was underpredicted by 0.7% and 4.9% without and with CDR, respectively. Utilizing anthropomorphic phantom recovery coefficient overpredicted the absorbed dose by 3% both with and without CDR. All dosimetry scenarios that incorporated PVC were within the calculated uncertainty of the activity. The uncertainties in the cumulative activity ranged from 23.6% to 106.4% for Jaszczak spheres ranging in volume from 0.5 to 16 ml. CONCLUSION: The accuracy of Monte Carlo-based dosimetry for 131 I RPT in HNC was validated with an anthropomorphic phantom. In this study, it was found that Jaszczak-based PVCs were sufficient. Future applications of the phantom could involve 3D printing and characterizing patient-specific volumes for more personalized RPT dosimetry estimates.

Dose Deposits from 90Y, 177Lu, 111In, and 161Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy.

UNLABELLED: Radiopharmaceutical therapy, traditionally limited to refractory metastatic cancer, is being increasingly used at earlier stages, such as for treating minimal residual disease. The aim of this study was to compare the effectiveness of (90)Y, (177)Lu, (111)In, and (161)Tb at irradiating micrometastases. (90)Y and (177)Lu are widely used ß(-)-emitting radionuclides. (161)Tb is a medium-energy ß(-) radionuclide that is similar to (177)Lu but emits a higher percentage of conversion and Auger electrons. (111)In emits γ-photons and conversion and Auger electrons. METHODS: We used the Monte Carlo code CELLDOSE to assess electron doses from a uniform distribution of (90)Y, (177)Lu, (111)In, or (161)Tb in spheres with diameters ranging from 10 mm to 10 µm. Because these isotopes differ in electron energy per decay, the doses were compared assuming that 1 MeV was released per µm(3), which would result in 160 Gy if totally absorbed. RESULTS: In a 10-mm sphere, the doses delivered by (90)Y, (177)Lu, (111)In, and (161)Tb were 96.5, 152, 153, and 152 Gy, respectively. The doses decreased along with the decrease in sphere size, and more abruptly so for (90)Y. In a 100-µm metastasis, the dose delivered by (90)Y was only 1.36 Gy, compared with 24.5 Gy for (177)Lu, 38.9 Gy for (111)In, and 44.5 Gy for (161)Tb. In cell-sized spheres, the dose delivered by (111)In and (161)Tb was higher than that of (177)Lu. For instance, in a 10-µm cell, (177)Lu delivered 3.92 Gy, compared with 22.8 Gy for (111)In and 14.1 Gy for (161)Tb. CONCLUSION: (177)Lu, (111)In, and (161)Tb might be more appropriate than (90)Y for treating minimal residual disease. (161)Tb is a promising radionuclide because it combines the advantages of a medium-energy ß(-) emission with those of Auger electrons and emits fewer photons than (111)In.