Determination of Critical Organ Doses with 177Lu Prostate-specific Membrane Antigen Dosimetry in Metastatic Prostate Cancer Treatment.

Aim: This study aimed to perform dosimetry in patients with metastatic prostate cancer treated with 177Lutetium (Lu) prostate-specific membrane antigen (PSMA)-617 radiopharmaceutical, calculating organ blood clearance and consequently determining the maximum tolerable treatment activity. Materials and Methods: Eighteen patients with metastatic prostate cancer were enrolled in the study. Patients were administered 5.55 gigabecquerel (GBq) of 177Lu-PSMA-617 radiopharmaceutical per treatment cycle through infusion. Blood samples (2 mL each) were collected at 2, 4, 6, 8, 18, 24, 36, and 44 h postinjection to assess the bone marrow absorbed dose. Organ doses were calculated using the OLINDA/EXM software based on scintigraphic images of the 18 patients who received 177Lu-PSMA-617. Results: The blood clearance of 177Lu-PSMA-617 radiopharmaceutical was determined to be bi-exponential. The mean absorbed doses for the parotid glands, kidneys, bone marrow, and liver were found to be 1.18 ± 0.27, 1.05 ± 0.3, 0.07 ± 0.05, and 0.31 ± 0.2 Gy/GBq, respectively. The radiation dose to the bone marrow was significantly lower than that to the kidneys and parotid glands. No dose limitations were necessary for kidneys and bone marrow in any of the patients. Conclusions: Our dosimetry results indicate that 177Lu-PSMA-617 therapy is safe in terms of radiation toxicity.

Enhanced Internal Dosimetry for Alimentary Tract Organs in Nuclear Medicine based on the ICRP Mesh-Type Reference Phantoms.

This study introduces a refined approach for more accurately estimating radiation doses to alimentary tract organs in nuclear medicine, by utilizing the ICRP pediatric and adult mesh-type reference computational phantoms (MRCPs) that improved the anatomical representation of these organs. Our initial step involved compiling a comprehensive dataset of electron Specific Absorbed Fractions (SAFs) for all source-target pairs of alimentary tract organs in both adult and pediatric phantoms, calculating SAFs for all cases in the present study only except those computed in the previous study for certain pediatric phantom cases. Subsequently, we determined S values for 1,252 radionuclides, facilitating dosimetry applications. The consistency of target and source masses for alimentary tract organs in the MRCPs with the reference values in ICRP Publication 89 led to noticeable differences in SAF, S values, and consequently, absorbed dose coefficients when compared to the stylized models in ICRP Publication 100. Notably, the S value ratios (MRCP/stylized) for selected radionuclides-11C, 18F, 68Ga, and 131I-ranged from 0.41 to 7.60. Particularly for therapeutic 131I-iodide in thyroid cancer, the use of MRCPs resulted in up to 1.49 times higher absorbed dose coefficients for the colon than those derived from stylized models, while the stomach dose coefficients decreased by a factor of 0.72. The application of our findings promises enhanced, more realistic dosimetry for alimentary tract organs, especially beneficial for radiopharmaceuticals likely to accumulate within these organs.

Program for Determining the Dosimetric Contribution of Tc-99m Biokinetics in Estimating the Dose to the Heart of a Male Adult.

Purpose: To calculate the contribution of absorbed dose by organs in the biokinetics of Tc-99m when used for radiodiagnosis of the adult male heart employing a Matlab program. Methods: The absorbed self-dose of the adult male heart and absorbed dose by organs in the biokinetics of the heart when administering Tc-99m are estimated using the MIRD formalism and the Cristy-Eckerman representation, which have been employed to develop the algorithm in Matlab. Results: The results indicate that electron capture emissions of 1.446 (mGy/MBq) and Auger electrons of 0.062 (mGy/MBq) are entirely directed towards the target organ (heart) and contribute 29.33% and 1.25% respectively to its total dose. Additionally, the dosimetric contributions of biokinetic organs correspond to characteristic radiation emissions and gamma photons at 2.578 (mGy/MBq) for Tc-99m, representing 52.29% of its total dose. Conclusion: These dosimetric contributions are significant in estimating the total absorbed dose by the heart in adult males and should not be disregarded.

A step toward simplified dosimetry of radiopharmaceutical therapy via SPECT frame duration reduction.

Despite being time-consuming, SPECT/CT data is necessary for accurate dosimetry in patient-specific radiopharmaceutical therapy. We investigated how reducing the frame duration (FD) during SPECT acquisition can simplify the dosimetry workflow for [177Lu]Lu-PSMA radioligand therapy (RLT). We aimed to determine the impact of shortened acquisition times on dosimetric precision. Three SPECT scans with FD of 20, 10, and 5 second/frame (sec/fr) were obtained 48 h post-RLT from one metastatic castration-resistant prostate cancer (mCRPC) patient's pelvis. Planar images at 4, 48, and 72 h post-therapy were used to calculate time-integrated activities (TIAs). Using accurate activity calibrations and GATE Monte Carlo (MC) dosimetry, absorbed doses in tumor lesions and kidneys were estimated. Dosimetry precision was assessed by comparing shorter FD results to the 20 sec/fr reference using relative percentage difference (RPD). We observed consistent calibration factors (CFs) across different FDs. Using the same CF, we obtained marginal RPD deviations less than 4% for the right kidney and tumor lesions and less than 7% for the left kidney. By reducing FD, simulation time was slightly decreased. This study shows we can shorten SPECT acquisition time in RLT dosimetry by reducing FD without sacrificing dosimetry accuracy. These findings pave the way for streamlined personalized internal dosimetry workflows.

Internal absorbed dose calculation in body organs due to injection of Rhenium-188 labeled to Mu-9 antibody.

The use of radiopharmaceuticals has gained a special place in the diagnosis and treatment of cancers and evaluation of the function of different organs of the body. In this study, the absorbed dose distribution of organs after injection of 188Re-Mu-9 has been investigated using MIRD method and MCNP-4C simulation code. The 188Re-Mu-9 labeled was injected the mouse body and the amount of 188Re-labeled accumulation was evaluated after 1, 4 and 2 4 h. Having a map of the distribution of radiopharmaceutical activity in the animal body, it is possible to convert it into a human model to obtain the internal dose received by 188Re-Mu-9 injection using the MIRD calculation method and the MCNP simulation code. According to the results of the study, the animal/human model can be acceptable method for dose estimation of antibody-based radiopharmaceuticals.

Mathematical complexities in radionuclide metabolic modelling: a review of ordinary differential equation kinetics solvers in biokinetic modelling.

Biokinetic models have been employed in internal dosimetry (ID) to model the human body's time-dependent retention and excretion of radionuclides. Consequently, biokinetic models have become instrumental in modelling the body burden from biological processes from internalized radionuclides for prospective and retrospective dose assessment. Solutions to biokinetic equations have been modelled as a system of coupled ordinary differential equations (ODEs) representing the time-dependent distribution of materials deposited within the body. In parallel, several mathematical algorithms were developed for solving general kinetic problems, upon which biokinetic solution tools were constructed. This paper provides a comprehensive review of mathematical solving methods adopted by some known internal dose computer codes for modelling the distribution and dosimetry for internal emitters, highlighting the mathematical frameworks, capabilities, and limitations. Further discussion details the mathematical underpinnings of biokinetic solutions in a unique approach paralleling advancements in ID. The capabilities of available mathematical solvers in computational systems were also emphasized. A survey of ODE forms, methods, and solvers was conducted to highlight capabilities for advancing the utilization of modern toolkits in ID. This review is the first of its kind in framing the development of biokinetic solving methods as the juxtaposition of mathematical solving schemes and computational capabilities, highlighting the evolution in biokinetic solving for radiation dose assessment.

Absorbed dose coefficients for pediatric differentiated thyroid cancer patients undergoing radioiodine therapy.

The escalating incidence of differentiated thyroid cancer (DTC) in pediatric patients and the resultant growing use of radioactive iodine (RAI) reinforce the need to evaluate radiation exposure to normal tissues and radiation-induced health risks in pediatric patients undergoing RAI therapy. In the current study, we calculated absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq-1) specific for pediatric patients with localized DTC undergoing RAI therapy following total thyroidectomy for use in epidemiological studies. We first modified previously-published biokinetic models for adult thyroid cancer patients to achieve a reasonable agreement with iodine biokinetics observed in pediatric patients or design principles addressed in the International Commission on Radiological Protection (ICRP) reference age-specific biokinetic models. We then combined the biokinetic models in conjunction withSvalues derived from ICRP reference pediatric voxel phantoms. The absorbed dose coefficients for pediatric patients were overall greater than those for adults with a ratio (pediatric/adult) up to 11.6 and rapidly decreased with increasing age. The sensitivity analysis showed that the renal clearance rate andSvalues may have the greatest impact on the absorbed dose coefficients with the rank correlation coefficients ranging from -0.53 to -0.82 (negative correlations) and from 0.51 to 0.80 (positive correlations), respectively. The results of the current study may be utilized in clinical or epidemiological studies to estimate organ-specific radiation absorbed doses and radiation-associated health risks among pediatric thyroid cancer patients.

Impact of deep learning-based multiorgan segmentation methods on patient-specific internal dosimetry in PET/CT imaging: A comparative study.

PURPOSE: Accurate and fast multiorgan segmentation is essential in image-based internal dosimetry in nuclear medicine. While conventional manual PET image segmentation is widely used, it suffers from both being time-consuming as well as subject to human error. This study exploited 2D and 3D deep learning (DL) models. Key organs in the trunk of the body were segmented and then used as a reference for networks. METHODS: The pre-trained p2p-U-Net-GAN and HighRes3D architectures were fine-tuned with PET-only images as inputs. Additionally, the HighRes3D model was alternatively trained with PET/CT images. Evaluation metrics such as sensitivity (SEN), specificity (SPC), intersection over union (IoU), and Dice scores were considered to assess the performance of the networks. The impact of DL-assisted PET image segmentation methods was further assessed using the Monte Carlo (MC)-derived S-values to be used for internal dosimetry. RESULTS: A fair comparison with manual low-dose CT-aided segmentation of the PET images was also conducted. Although both 2D and 3D models performed well, the HighRes3D offers superior performance with Dice scores higher than 0.90. Key evaluation metrics such as SEN, SPC, and IoU vary between 0.89-0.93, 0.98-0.99, and 0.87-0.89 intervals, respectively, indicating the encouraging performance of the models. The percentage differences between the manual and DL segmentation methods in the calculated S-values varied between 0.1% and 6% with a maximum attributed to the stomach. CONCLUSION: The findings prove while the incorporation of anatomical information provided by the CT data offers superior performance in terms of Dice score, the performance of HighRes3D remains comparable without the extra CT channel. It is concluded that both proposed DL-based methods provide automated and fast segmentation of whole-body PET/CT images with promising evaluation metrics. Between them, the HighRes3D is more pronounced by providing better performance and can therefore be the method of choice for 18F-FDG-PET image segmentation.

The contest between internal and external-beam dosimetry: The Zeno's paradox of Achilles and the tortoise.

Radionuclide therapy, also called molecular radiotherapy (MRT), has come of age, with several novel radiopharmaceuticals being approved for clinical use or under development in the last decade. External beam radiotherapy (EBRT) is a well-established treatment modality, with about half of all oncologic patients expected to receive at least one external radiation treatment over their disease course. The efficacy and the toxicity of both types of treatment rely on the interaction of radiation with biological tissues. Dosimetry played a fundamental role in the scientific and technological evolution of EBRT, and absorbed doses to the target and to the organs at risk are calculated on a routine basis. In contrast, in MRT the usefulness of internal dosimetry has long been questioned, and a structured path to include absorbed dose calculation is missing. However, following a similar route of development as EBRT, MRT treatments could probably be optimized in a significant proportion of patients, likely based on dosimetry and radiobiology. In the present paper we describe the differences and the similarities between internal and external-beam dosimetry in the context of radiation treatments, and we retrace the main stages of their development over the last decades.

Deep Learning-Based Delayed PET Image Synthesis from Corresponding Early Scanned PET for Dosimetry Uptake Estimation.

The acquisition of in vivo radiopharmaceutical distribution through imaging is time-consuming due to dosimetry, which requires the subject to be scanned at several time points post-injection. This study aimed to generate delayed positron emission tomography images from early images using a deep-learning-based image generation model to mitigate the time cost and inconvenience. Eighteen healthy participants were recruited and injected with [18F]Fluorodeoxyglucose. A paired image-to-image translation model, based on a generative adversarial network (GAN), was used as the generation model. The standardized uptake value (SUV) mean of the generated image of each organ was compared with that of the ground-truth. The least square GAN and perceptual loss combinations displayed the best performance. As the uptake time of the early image became closer to that of the ground-truth image, the translation performance improved. The SUV mean values of the nominated organs were estimated reasonably accurately for the muscle, heart, liver, and spleen. The results demonstrate that the image-to-image translation deep learning model is applicable for the generation of a functional image from another functional image acquired from normal subjects, including predictions of organ-wise activity for specific normal organs.

Mathematical solutions in internal dose assessment: A comparison of Python-based differential equation solvers in biokinetic modeling.

In biokinetic modeling systems employed for radiation protection, biological retention and excretion have been modeled as a series of discretized compartments representing the organs and tissues of the human body. Fractional retention and excretion in these organ and tissue systems have been mathematically governed by a series of coupled first-order ordinary differential equations (ODEs). The coupled ODE systems comprising the biokinetic models are usually stiff due to the severe difference between rapid and slow transfers between compartments. In this study, the capabilities of solving a complex coupled system of ODEs for biokinetic modeling were evaluated by comparing different Python programming language solvers and solving methods with the motivation of establishing a framework that enables multi-level analysis. The stability of the solvers was analyzed to select the best performers for solving the biokinetic problems. A Python-based linear algebraic method was also explored to examine how the numerical methods deviated from an analytical or semi-analytical method. Results demonstrated that customized implicit methods resulted in an enhanced stable solution for the inhaled60Co (Type M) and131I (Type F) exposure scenarios for the inhalation pathway of the International Commission on Radiological Protection (ICRP) Publication 130 Human Respiratory Tract Model (HRTM). The customized implementation of the Python-based implicit solvers resulted in approximately consistent solutions with the Python-based matrix exponential method (expm). The differences generally observed between the implicit solvers andexpmare attributable to numerical precision and the order of numerical approximation of the numerical solvers. This study provides the first analysis of a list of Python ODE solvers and methods by comparing their usage for solving biokinetic models using the ICRP Publication 130 HRTM and provides a framework for the selection of the most appropriate ODE solvers and methods in Python language to implement for modeling the distribution of internal radioactivity.

First-in-human study of a novel cell death tracer [99mTc]Tc-Duramycin: safety, biodistribution and radiation dosimetry in healthy volunteers.

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 selective tumor accumulation early after the onset of anticancer therapy. In this first-in-human study, we report the safety, biodistribution and internal radiation dosimetry of [99mTc]Tc-Duramycin in healthy human volunteers. RESULTS: Six healthy volunteers (3 males, 3 females) were injected intravenously with [99mTc]Tc-Duramycin (dose: 6 MBq/kg; 473 ± 36 MBq). [99mTc]Tc-Duramycin was well tolerated in all subjects, with no serious adverse events reported. Following injection, a 30-min dynamic planar imaging of the abdomen was performed, and whole-body (WB) planar scans were acquired at 1, 2, 3, 6 and 23 h post-injection (PI), with SPECT acquisitions after each WB scan and one low-dose CT after the first SPECT. In vivo 99mTc activities were determined from semi-quantitative analysis of the images, and time-activity curves were generated. Residence times were calculated from the dynamic and WB planar scans. The mean effective dose was 7.61 ± 0.75 µSv/MBq, with the kidneys receiving the highest absorbed dose (planar analysis: 43.82 ± 4.07 µGy/MBq, SPECT analysis: 19.72 ± 3.42 µGy/MBq), followed by liver and spleen. The median effective dose was 3.61 mSv (range, 2.85-4.14). The tracer cleared slowly from the blood (effective half-life of 2.0 ± 0.4 h) due to high plasma protein binding with < 5% free tracer 3 h PI. Excretion was almost exclusively renal. CONCLUSION: [99mTc]Tc-Duramycin demonstrated acceptable dosimetry (< 5 mSv) and a favorable safety profile. Due to slow blood clearance, optimal target-to-background ratios are expected 5 h PI. These data support the further assessment of [99mTc]Tc-Duramycin for clinical treatment response evaluation. TRIAL REGISTRATION: NCT05177640, Registered April 30, 2021, https://clinicaltrials.gov/study/NCT05177640 .

Comparison between InterDosi and MCNP in the estimation of photon SAFs on a series of ICRP pediatric voxelized phantoms.

In the present work, a new Monte Carlo Geant4 based code called InterDosi 1.0, was used to simulate specific absorbed fractions (SAFs) in the six reference pediatric voxel-based phantoms developed by the International Commission on Radiological Protection (ICRP). The aim of this study was to assess the ability of this code to estimate SAFs in a variety of voxel-based phantoms. A large number of photon SAFs were calculated for pairs of organs corresponding to three sources and 170 target organs/regions. A total of 108 initial photons were uniformly emitted from the source organs with eight discrete energies. In order to speed up the calculation of SAFs, Monte Carlo multithreaded simulations were started on a workstation with 12 threads, and a Geant4 tracking optimization technique was applied that consists in skipping the voxel boundaries when two adjacent voxels share the same material, which seems to reduce the simulation time by an average of approximately 36%. The results showed good agreement with the reference data produced through the MCNP 2.7 code, with average and maximum absolute discrepancies of 0.5% and 7.68%, respectively. We concluded that these results confirm the feasibility of InterDosi code to perform photon internal dosimetry calculations at a voxel level.

Impact of Single-Time-Point Estimates of 177Lu-PRRT Absorbed Doses on Patient Management: Validation of a Trained Multiple-Linear-Regression Model in 159 Patients and 477 Therapy Cycles.

Dosimetry after 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) enables estimation of radiation doses absorbed by normal organs and target lesions. This process is time-consuming and requires multiple posttreatment studies on several subsequent days. In a previous study, we described a newly developed multiple-linear-regression model to predict absorbed doses (ADs) from a single-time-point (STP) posttreatment study acquired 168 h after the first infusion and 24 h after the following ones, with similar results to the standard multiple-time-point (MTP) protocol. The present study aimed to validate this model in a large patient cohort and to assess whether STP dosimetry affects patient management decisions compared with our MTP protocol. Methods: Quantitative 177Lu-DOTATATE SPECT/CT post-PRRT data from 159 consecutive patients (172 therapies, 477 therapy cycles) were retrospectively analyzed. ADs obtained from an STP model were compared with those obtained using an MTP model. We evaluated the impact of the STP model on the decision on whether PRRT should be stopped because of an expected kidney AD exceeding the safety threshold. We hypothesized that patient management based on the STP model does not differ from that based on the MTP model in at least 90% of the cases. Results: There was no difference in management decisions between the MTP and STP models in 170 of 172 therapies (98.8%). A Fisher χ2 test for combined probabilities produced a composite P value of 0.0003. Mean cumulative AD relative differences between the STP and MTP models were 0.8% ± 8.0%, -7.7% ± 4.8%, 0.0% ± 11.4%, -2.8% ± 6.3%, and -2.1% ± 18.4% for kidneys, bone marrow, liver, spleen, and tumors, respectively (Pearson r = 0.99 for all), for patients who underwent 4 therapy cycles. Similar results were obtained with fewer therapy cycles. Conclusion: Estimated radiation ADs and patient management decisions were similar with the STP and MTP models. The STP model can simplify the dosimetry process while also reducing scanner and staff time and improving patient comfort.

Internal occupational dosimetry for the occupational worker exposed to [18F] FDG from the Cyclotron-PET/CT Laboratory of the Universidad de Costa Rica / Dosimetría ocupacional interna para el personal trabajador expuesto a [18F] FDG del ciclotrón-PET/CT en el Laboratorio de la Universidad de Costa Rica

ABSTRACT: The aim of this work is to provide a methodology for evaluating the committed effective dose E(50) due to the incorporation of [18F] FDG in the occupationally exposed worker (OEW) of the Cyclotron-PET/CT Laboratory of the Centro de Investigación en Ciencias Atómicas, Nucleares y Moleculares (CICANUM) at Universidad de Costa Rica using in vivo measurements. The measurement system was calibrated to perform in vivo measurements and defined as the corresponding bioassay function for the radiopharmaceutical used. The conversion factor was assessed with a known activity of 18F in the geometry and measurement time established. Among the most relevant results, the measurement parameters and the calibration procedure were defined. A value of 1.73 x 103 Bq/cps for in vivo brain measurements was obtained as a conversion factor. This study provides a methodology, to evaluate the committed effective dose due to the incorporation of 18F-FDG in a radionuclide production and diagnostic center

A machine learning-based model for a dose point kernel calculation.

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 sources were calculated using the FLUKA Monte Carlo (MC) code for many materials of clinical interest and initial energies ranging from 10 to 3000 keV. Regressor Chains (RC) with three different coefficients regularization/shrinkage models were used as base regressors. Electron monoenergetic scaled DPKs (sDPKs) were used to assess the corresponding sDPKs for beta emitters typically used in nuclear medicine, which were compared against reference published data. Finally, the beta emitters sDPK were applied to a patient-specific case calculating the Voxel Dose Kernel (VDK) for a hepatic radioembolization treatment with [Formula: see text]Y. RESULTS: The three trained machine learning models demonstrated a promising capacity to predict the sDPK for both monoenergetic emissions and beta emitters of clinical interest attaining differences lower than [Formula: see text] in the mean average percentage error (MAPE) as compared with previous studies. Furthermore, differences lower than [Formula: see text] were obtained for the absorbed dose in patient-specific dosimetry comparing against full stochastic MC calculations. CONCLUSION: An ML model was developed to assess dosimetry calculations in nuclear medicine. The implemented approach has shown the capacity to accurately predict the sDPK for monoenergetic beta sources in a wide range of energy in different materials. The ML model to calculate the sDPK for beta-emitting radionuclides allowed to obtain VDK useful to achieve reliable patient-specific absorbed dose distributions required short computation times.

Internal dosimetry of 64Cu-DOX-loaded microcapsules by Monte Carlo method.

Some of the issues regarding introducing new radiocompounds in nuclear medicine are the distribution patterns, delivered dose to different organs, diagnostic abilities and side effects. In this study, in order to assess the biodistribution of 64Cu-DOX-loaded microcapsules, rats were IV-injected with the microcapsules, and 1, 4, 14, and 24 h later, the activities of the targeted organs were measured (%ID/g). The accumulated activities were achieved by %ID/g curves, and S-factors were obtained by MCNP outputs. The MIRD formulation and Monte Carlo method were used to determine the absorbed dose in the target organs. The biodistribution data and PET-CT images showed that the lungs were where the majority of activity was seen. According to MIRD and MCNP, the maximum dose delivered in the lungs was 5.79E+01 mGy/MBq and 4.70E+01 mGy/MBq, respectively. Also, the effective dose was 1.2E+01 for MIRD and 8.31E+00 mSv/MBq for MCNP. These results indicate that 64Cu-DOX microcapsules can be considered a new radiocompound in pulmonary imaging, and MCNP simulation can be a reliable method for internal dosimetry.

18F-PSMA-1007 salivary gland dosimetry: comparison between different methods for dose calculation and assessment of inter- and intra-patient variability.

Objective. Simplified calculation approaches and geometries are usually adopted for salivary glands (SGs) dosimetry. Our aims were (i) to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following [18F]-PSMA-1007 injection, and (ii) to assess the AD variation across patients and single SG components. Approach. Five patients with prostate cancer underwent sequential positron-emission tomography/computed tomography (PET/CT) acquisitions of the head and neck, 0.5, 2 and 4 h after [18F]-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PET images were used to derive Time-Integrated Activity Coefficients. Average ADs to single SG components or total SG (tSG) were calculated with the following methods: (i) direct Monte Carlo simulation with GATE/GEANT4 considering radioactivity in the entire PET/CT field-of-view (MC) or in the SGs only (MCsgo); (ii) spherical model (SM) of OLINDA/EXM 2.1, adopting either patient-specific or standard ICRP89 organ masses (SMstd); (iii) ellipsoidal model (EM); (iv) MIRD approach with organS-factors from OLINDA/EXM 2.1 and OpenDose collaboration, with or without contribution from cross irradiation originating outside the SGs. The maximum percent AD difference across SG components (δmax) and across patients (Δmax) were calculated.Main results. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences ranging between -11.9% and -30.5%).δmaxvalues were never below 25%. The highestδmax(=702%) was obtained with SMstd. Concerning tSG, results within 10% of the MC were obtained only if cross-irradiation from the remainder of the body or from the remainder of the head was accounted for. The Δmaxranged between 58% and 78% across patients.Significance. Simple geometrical models for SG dosimetry considerably underestimated ADs compared to MC, particularly if neglecting cross-irradiation from neighboring regions. Specific masses of single SG components should always be considered given their large intra- and inter-patient variability.

S-values estimation of positron-emitting radionuclides in the ICRP voxel-based adult male organs using a new Geant4-based code DoseCalcs: validation study.

Identifying the organs and tissues at risk from internal radiation exposure caused by radiopharmaceuticals requires determining the absorbed dose. The absorbed dose for radiopharmaceuticals is calculated by multiplying cumulated activity in source organs by the S-value, a crucial quantity that connects the energy deposited in the target organ and the emitting source one. It is defined as the ratio of absorbed energy in the target organ per unit of mass and unit of nuclear transition in the source organ. In this study, we used a new Geant4-based code called DoseCalcs to estimate the S-values for four positron-emitting radionuclides ([Formula: see text]C, [Formula: see text]N, [Formula: see text]O, and [Formula: see text]F) using decay and energy data from International Commission on Radiological Protection (ICRP) Publication 107. Twenty-three regions were simulated as radiation sources in the ICRP voxelized adult model developed in ICRP Publication 110. The Livermore physics packages were tailored to radionuclide photon mono-energy and [Formula: see text]-mean energy. The estimated S-values based on [Formula: see text]-mean energy show good agreement with those in the OpenDose data whose values were calculated using the full [Formula: see text] spectrum. The results provide new S-values data for selected source regions; hence, they could be used for comparison and adult-patient dose estimation.

Preclinical PET Imaging and Toxicity Study of a 68Ga-Functionalized Polymeric Cardiac Blood Pool Agent.

Cardiac blood pool imaging is currently performed almost exclusively with 99mTc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope 68Ga is used, it can be applied repeatedly on the same day-for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with 68Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the 99mTc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application.