Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

PURPOSE: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. MATERIALS AND METHODS: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. RESULTS: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. CONCLUSION: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP.

BACKGROUND: 4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [11C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity. To prepare for the translation to human studies, we developed a cGMP-compatible automated radiosynthesis protocol and evaluated the whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP in non-human primates (NHPs). METHODS: Automated radiosynthesis was carried out using a GE TRACERlab FX-C Pro synthesis module. One male and one female adult rhesus macaques were used in the study. A high-resolution CT from cranial vertex to knee was acquired. PET data were collected using a dynamic acquisition protocol with four bed positions and 13 passes over a total scan time of ~ 150 min. Based on the CT and PET images, volumes of interest (VOIs) were manually drawn for selected organs. Non-decay corrected time-activity curves (TACs) were extracted for each VOI. Radiation dosimetry and effective dose were calculated from the integrated TACs using OLINDA software. RESULTS: Fully automated radiosynthesis of [11C]3MeO4AP was achieved with 7.3 ± 1.2% (n = 4) of non-decay corrected radiochemical yield within 38 min of synthesis and purification time. [11C]3MeO4AP distributed quickly throughout the body and into the brain. The organs with highest dose were the kidneys. The average effective dose of [11C]3MeO4AP was 4.0 ± 0.6 µSv/MBq. No significant changes in vital signs were observed during the scan. CONCLUSION: A cGMP-compatible automated radiosynthesis of [11C]3MeO4AP was developed. The whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP was successfully evaluated in NHPs. [11C]3MeO4AP shows lower average effective dose than [18F]3F4AP and similar average effective dose as other carbon-11 tracers.

Retrospective case-control study on radiation dose for uterine artery embolization procedures.

INTRODUCTION: Uterine artery embolization is performed in pre-menopausal women. Understanding the contribution of radiation dose at each stage of the procedure is important for potential dose reduction. The aim was to retrospectively analyse radiation dose on a per-procedural-stage basis, comparing digital subtraction angiography (DSA) and conventional roadmap (CRM). METHODS: Group A consisted of 50 patients where DSA was used for road mapping at all stages: (I) Aortogram, (II) Left internal iliac artery (IIA) DSA, (III) Left uterine artery (UA) DSA, (IV) Right IIA DSA and (V) Right UA DSA. Group B included 50 patients, where CRM was used for road mapping at stages (II) and (IV). RESULTS: For Group A, mean total dose-area product (DAP) was 39.7 Gy·cm2; mean DAP for each stage were (I) Aortogram = 3.4 Gy·cm2, (II) Left IIA DSA = 5.9 Gy·cm2, (III) Left UA DSA = 3.2 Gy·cm2, (IV) Right IIA DSA = 5.5 Gy·cm2 and (V) Right UA DSA = 3.0 Gy·cm2. For Group B, mean total DAP was 33.6 Gy·cm2, mean DAP for each stage were (I) Aortogram = 3.3 Gy·cm2, (II) Left IIA CRM = 1.5 Gy·cm2, (III) Left UA DSA = 3.3 Gy·cm2, (IV) Right IIA CRM = 1.5 Gy·cm2 and (V) Right UA DSA = 3.3 Gy·cm2. Fluoroscopy time was 10 and 9.4 min for Groups A and B, respectively. CONCLUSION: The highest road-mapping radiation dose contribution was from bilateral IIA DSA. The use of CRM, intermittent fluoroscopy and elimination of the aortogram is recommended to further reduce procedural radiation dose.

A study of polarity effect for various ionization chambers in kilovoltage x-ray beams.

BACKGROUND: Ionization chambers play an essential role in dosimetry measurements for kilovoltage (kV) x-ray beams. Despite their widespread use, there is limited data on the absolute values for the polarity correction factors across a range of commonly employed ionization chambers. PURPOSE: This study aimed to investigate the polarity effects for five different ionization chambers in kV x-ray beams. METHODS: Two plane-parallel chambers being the Advanced Markus and Roos and three cylindrical chambers; 3D PinPoint, Semiflex and Farmer chamber (PTW, Freiburg, Germany), were employed to measure the polarity correction factors. The kV x-ray beams were produced from an Xstrahl 300 unit (Xstrahl Ltd., UK). All measurements were acquired at 2 cm depth in a PTW-MP1 water tank for beams between 60 kVp (HVL 1.29 mm Al) and 300 kVp (HVL 3.08 mm Cu), and field sizes of 2-10 cm diameter for 30 cm focus-source distance (FSD) and 4 × 4 cm2 - 20 × 20 cm2 for 50 cm FSD. The ionization chambers were connected to a PTW-UNIDOS electrometer, and the polarity effect was determined using the AAPM TG-61 code of practice methodology. RESULTS: The study revealed significant polarity effects in ionization chambers, especially in those with smaller volumes. For the plane-parallel chambers, the Advanced Markus chamber exhibited a maximum polarity effect of 2.5%, whereas the Roos chamber showed 0.3% at 150 KVp with the 10 cm circular diameter open-ended applicator. Among the cylindrical chambers at the same beam energy and applicator, the Pinpoint chamber exhibited a 3% polarity effect, followed by Semiflex with 1.7%, and Farmer with 0.4%. However, as the beam energy increased to 300 kVp, the polarity effect significantly increased reaching 8.5% for the Advanced Markus chamber and 13.5% for the PinPoint chamber at a 20 × 20 cm2 field size. Notably, the magnitude of the polarity effect increased with both the field size and beam energy, and was significantly influenced by the size of the chamber's sensitive volume. CONCLUSIONS: The findings demonstrate that ionization chambers can exhibit substantial polarity effects in kV x-ray beams, particularly for those chambers with smaller volumes. Therefore, it is important to account for polarity corrections when conducting relative dose measurements in kV x-ray beams to enhance the dosimetry accuracy and improve patient dose calculations.

Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects.

BACKGROUND: Tau pathology plays a crucial role in neurodegeneration diseases including Alzheimer's disease (AD) and non-AD diseases such as progressive supranuclear palsy. Tau positron emission tomography (PET) is an in-vivo and non-invasive medical imaging technique for detecting and visualizing tau deposition within a human brain. In this work, we aim to investigate the biodistribution of the dosimetry in the whole body and various organs for the [18F]Florzolotau tau-PET tracer. A total of 12 healthy controls (HCs) were enrolled at Chang Gung Memorial Hospital. All subjects were injected with approximately 379.03 ± 7.03 MBq of [18F]Florzolotau intravenously, and a whole-body PET/CT scan was performed for each subject. For image processing, the VOI for each organ was delineated manually by using the PMOD 3.7 software. Then, the time-activity curve of each organ was acquired by optimally fitting an exponential uptake and clearance model using the least squares method implemented in OLINDA/EXM 2.1 software. The absorbed dose for each target organ and the effective dose were finally calculated. RESULTS: From the biodistribution results, the elimination of [18F]Florzolotau is observed mainly from the liver to the intestine and partially through the kidneys. The highest organ-absorbed dose occurred in the right colon wall (255.83 µSv/MBq), and then in the small intestine (218.67 µSv/MBq), gallbladder wall (151.42 µSv/MBq), left colon wall (93.31 µSv/MBq), and liver (84.15 µSv/MBq). Based on the ICRP103, the final computed effective dose was 34.9 µSv/MBq with CV of 10.07%. CONCLUSIONS: The biodistribution study of [18F]Florzolotau demonstrated that the excretion of [18F]Florzolotau are mainly through the hepatobiliary and gastrointestinal pathways. Therefore, a routine injection of 370 MBq or 185 MBq of [18F]Florzolotau leads to an estimated effective dose of 12.92 or 6.46 mSv, and as a result, the radiation exposure to the whole-body and each organ remains within acceptable limits and adheres to established constraints. TRIAL REGISTRATION: Retrospectively Registered at Clinicaltrials.gov (NCT03625128) on 12 July, 2018, https://clinicaltrials.gov/study/NCT03625128 .

Physics and small-scale dosimetry of α $\alpha$ -emitters for targeted radionuclide therapy: The case of 211 At $

BACKGROUND: Monte Carlo simulations have been considered for a long time the gold standard for dose calculations in conventional radiotherapy and are currently being applied for the same purpose in innovative radiotherapy techniques such as targeted radionuclide therapy (TRT). PURPOSE: We present in this work a benchmarking study of the latest version of the Transport d'Ions Lourds Dans l'Aqua & Vivo (TILDA-V ) Monte Carlo track structure code, highlighting its capabilities for describing the full slowing down of α $\alpha$ -particles in water and the energy deposited in cells by α $\alpha$ -emitters in the context of TRT. METHODS: We performed radiation transport simulations of α $\alpha$ -particles (10 keV u - 1 ${\rm u}^{-1}$ -100 MeV u - 1 ${\rm u}^{-1}$ ) in water with TILDA-V and the Particle and Heavy Ion Transport code System (PHITS) version 3.33. We compared the predictions of each code in terms of track parameters (stopping power, range and radial dose profiles) and cellular S-values of the promising radionuclide astatine-211 ( 211 At $^{211}{\rm At}$ ). Additional comparisons were made with available data in the literature. RESULTS: The stopping power, range and radial dose profiles of α $\alpha$ -particles computed with TILDA-V were in excellent agreement with other calculations and available data. Overall, minor differences with PHITS were ascribed to phase effects, that is, related to the use of interaction cross sections computed for water vapor or liquid water. However, important discrepancies were observed in the radial dose profiles of monoenergetic α $\alpha$ -particles, for which PHITS results showed a large underestimation of the absorbed dose compared to other codes and experimental data. The cellular S-values of 211 At $^{211}{\rm At}$ computed with TILDA-V  agreed within 4% with the values predicted by PHITS and MIRDcell. CONCLUSIONS: The validation of the TILDA-V code presented in this work opens the possibility to use it as an accurate simulation tool for investigating the interaction of α $\alpha$ -particles in biological media down to the nanometer scale in the context of medical research. The code may help nuclear medicine physicians in their choice of α $\alpha$ -emitters for TRT. Further research will focus on the application of TILDA-V for quantifying radioinduced damage on the deoxyribonucleic acid (DNA) molecule.

A prototype scintillator real-time beam monitor for ultra-high dose rate radiotherapy.

BACKGROUND: FLASH Radiotherapy (RT) is an emergent cancer RT modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. PURPOSE: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: (1) large area coverage; (2) a low mass profile; (3) a linear response over a broad dynamic range; (4) radiation hardness; (5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation dosimetry and excellent spatial resolution. METHODS: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ∼10 cm. A field programmable gate array (FPGA) data acquisition system generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital RT clinic with electron beams. RESULTS: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 min at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude versus beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of >40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 µm. Tests of the firmware beta version show successful operation at 20 000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. CONCLUSIONS: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

A model for estimating peak skin dose in CT.

In interventional radiology patient care can be improved by accurately assessing peak skin dose (PSD) from procedures, as it is the main predictor for tissue-reactions such as erythema. Historically, high skin dose procedures performed in radiology departments were almost exclusively planar fluoroscopy. However, with the increase in use of technologies involving repeated or adjacent computed tomography (CT) such as CT fluoroscopy and multi-modality rooms, the peak skin dose delivered by CT needs to be considered. In this paper, a model to estimate the PSD delivered to a patient undergoing CT has been developed to assist in determining the overall PSD. This model relates the PSD to the device-reported CT Dose Index (CTDIvol) by accounting for a variety of CT technique and patient factors. It includes a novel method for estimating dose contributions as a function of patient or phantom size, scanner geometry, and physical measurement of lateral and depth-based beam profiles. Physical measurements of PSD using radiochromic film on several phantoms have been used to determine needed model parameters. The resulting fitted model was found to agree with measured data to a standard deviation of 5.1% for the data used to fit the model, and 6.8% for measurements that were not used for fitting the model. Two methods for adapting the model for specific scanners are provided, one based on local PSD measurements with radiochromic film and another using CTDIvol measurements. The model, when suitably adapted, can accurately assess individual patients' CT PSD. This information can be integrated with radiation exposure data from other modalities, such as planar fluoroscopy, to predict the overall risk of tissue reactions, allowing for more tailored patient care.

Simplified image-based dosimetry using planar images and patient-specific S-values.

BACKGROUND: Single time point measurement approach and hybrid dosimetry were proposed to simplify the dosimetry process. It is anticipated that utilizing patient-specific S-value would enable more accurate dosimetry assessment based on imaging compared to using the conventional MIRD S-values. PURPOSE: We performed planar image-based dosimetry scaled with a single SPECT image for the entire treatment cycle using patient-specific S-values (PSS dosimetry) of organs. PSS dosimetry could further simplify the dosimetry procedure compared with a conventional 2D planar/3D SPECT hybrid dosimetry, as PSS dosimetry requires only one SPECT/CT image for the treatment of the entire cycle, whereas the conventional hybrid dosimetry requires a SPECT/CT image for each treatment cycle. METHODS: 177Lu-DOTATATE SPECT/CT and planar image datasets acquired from Seoul National University Hospital (SNUH, Seoul, Republic of Korea) were utilized for the evaluation. Images were acquired 4, 24, 48, and 120 h after patients' intravenous injection of 177Lu-DOTATATE. Dose estimations based on a Monte Carlo (MC) simulation using the Geant4 Application for Emission Tomography (GATE) (v.8.2) were considered as the reference. Planar image-based dosimetry scaled with a single SPECT image was performed using the patient-specific S-value (PSS). Briefly, the CT image was considered as the patient's anatomical reference and PSSs were quantified using the multiple voxel S-value (VSV) method. Then, PSS dosimetry was performed by obtaining activity information from sequential planar images and a scaling factor derived from a single SPECT/planar image pair. Hybrid dosimetry using sequential planar images and a single SPECT image was performed for comparison. The absorbed doses of the kidneys, bone marrow (BM) in the lumbar spine, liver, and spleen calculated using the PSS and hybrid dosimetries were compared with the reference MC results. RESULTS: The mean differences (MDs) of the self-absorption S-values between S-value of OLINDA/EXM and PSS for the kidneys, liver, and spleen were -0.04%, -2.39%, and -2.62%, respectively. However, the differences in the self-absorption S-values were significantly higher for the BM (84.99%) and the remainder of the body (ROB) (280.84%). The absorbed doses estimated by the PSS and hybrid dosimetries showed relatively high errors compared with MC simulation result, regardless of the organ. In contrast, the PSS and hybrid dosimetries produced similar dose estimates. For the entire cycles of the treatment, the MDs of absorbed doses between PSS and hybrid dosimetries were -3.31%, -6.04%, 3.37%, and -2.17% for the kidneys, BM, liver, and spleen, respectively. Through a correlation analysis and the Wilcoxon signed-rank test, we concluded that there was no significant difference between the results obtained by the two dosimetry methods. CONCLUSIONS: As the PSS was derived using CT images with actual anatomical information and organ-specific volume of interest (VOI), PSS dosimetry provided reliable results. PSS dosimetry was robust in estimating the absorbed dose for the later treatment cycles. Therefore, PSS dosimetry outperformed hybrid dosimetry in terms of dose estimation for a greater number of treatment cycles.

Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest.

OBJECTIVES: This study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. METHODS: Eleven healthy subjects (eight men and three women) received intravenous XTR004 (239-290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. RESULTS: In the first 0-12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. CONCLUSIONS: XTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

Radioactive seed localization is a safe and effective tool for breast cancer surgery: an evaluation of over 25,000 cases.

Radioactive seed localization (RSL) provides a precise and efficient method for removing non-palpable breast lesions. It has proven to be a valuable addition to breast surgery, improving perioperative logistics and patient satisfaction. This retrospective review examines the lessons learned from a high-volume cancer center's RSL program after 10 years of practice and over 25 000 cases. We provide an updated model for assessing the patient's radiation dose from RSL seed implantation and demonstrate the safety of RSL to staff members. Additionally, we emphasize the importance of various aspects of presurgical evaluation, surgical techniques, post-surgical management, and regulatory compliance for a successful RSL program. Notably, the program has reduced radiation exposure for patients and medical staff.

Radiation exposure in augmented fluoroscopic bronchoscopy procedures: a comprehensive analysis for patients and physicians.

Cancer is a major health challenge and causes millions of deaths worldwide each year, and the incidence of lung cancer has increased. Augmented fluoroscopic bronchoscopy (AFB) procedures, which combine bronchoscopy and fluoroscopy, are crucial for diagnosing and treating lung cancer. However, fluoroscopy exposes patients and physicians to radiation, and therefore, the procedure requires careful monitoring. The National Council on Radiation Protection and Measurement and the International Commission on Radiological Protection have emphasised the importance of monitoring patient doses and ensuring occupational radiation safety. The present study evaluated radiation doses during AFB procedures, focusing on patient skin doses, the effective dose, and the personal dose equivalent to the eye lens for physicians. Skin doses were measured using thermoluminescent dosimeters. Peak skin doses were observed on the sides of the patients' arms, particularly on the side closest to the x-ray tube. Differences in the procedures and experience of physicians between the two hospitals involved in this study were investigated. AFB procedures were conducted more efficiently at Hospital A than at Hospital B, resulting in lower effective doses. Cone-beam computed tomography (CT) contributes significantly to patient effective doses because it has higher radiographic parameters. Despite their higher radiographic parameters, AFB procedures resulted in smaller skin doses than did image-guided interventional and CT fluoroscopy procedures. The effective doses differed between the two hospitals of this study due to workflow differences, with cone-beam CT playing a dominant role. No significant differences in left and right eyeHp(3) values were observed between the hospitals. For both hospitals, theHp(3) values were below the recommended limits, indicating that radiation monitoring may not be required for AFB procedures. This study provides insights into radiation exposure during AFB procedures, concerning radiation dosimetry, and safety for patients and physicians.

A first-in-man study of [18F] FEDAC: a novel PET tracer for the 18-kDa translocator protein.

PURPOSE: N-benzyl-N-methyl-2-[7, 8-dihydro-7-(2-[18F] fluoroethyl) -8-oxo-2-phenyl-9H-purin-9-yl] acetamide ([18F] FEDAC) is a novel positron emission tomography (PET) tracer that targets the translocator protein (TSPO; 18 kDa) in the mitochondrial outer membrane, which is known to be upregulated in various diseases such as malignant tumors, neurodegenerative diseases, and neuroinflammation. This study presents the first attempt to use [18F]FEDAC PET/CT and evaluate its biodistribution as well as the systemic radiation exposure to the radiotracer in humans. MATERIALS AND METHODS: Seventeen whole-body [18F]FEDAC PET/CT (injected dose, 209.1 ± 6.2 MBq) scans with a dynamic scan of the upper abdomen were performed in seven participants. Volumes of interest were assigned to each organ, and a time-activity curve was created to evaluate the biodistribution of the radiotracer. The effective dose was calculated using IDAC-Dose 2.1. RESULTS: Immediately after the intravenous injection, the radiotracer accumulated significantly in the liver and was subsequently excreted into the gastrointestinal tract through the biliary tract. It also showed high levels of accumulation in the kidneys, but showed minimal migration to the urinary bladder. Thus, the liver was the principal organ that eliminated [18F] FEDAC. Accumulation in the normal brain tissue was minimal. The effective dose estimated from biodistribution in humans was 19.47 ± 1.08 µSv/MBq, and was 3.60 mSV for 185 MBq dose. CONCLUSION: [18F]FEDAC PET/CT provided adequate image quality at an acceptable effective dose with no adverse effects. Therefore, [18F]FEDAC may be useful in human TSPO-PET imaging.

Deep transformer-based personalized dosimetry from SPECT/CT images: a hybrid approach for [177Lu]Lu-DOTATATE radiopharmaceutical therapy.

PURPOSE: Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely employed. However, with the rapid advancement of deep learning (DL) algorithms, there has been an increasing interest in leveraging the calculation speed and automation capabilities for different tasks. We aimed to develop a hybrid transformer-based deep learning (DL) model that incorporates a multiple voxel S-value (MSV) approach for voxel-level dosimetry in [177Lu]Lu-DOTATATE therapy. The goal was to enhance the performance of the model to achieve accuracy levels closely aligned with Monte Carlo (MC) simulations, considered as the standard of reference. We extended our analysis to include MIRD formalisms (SSV and MSV), thereby conducting a comprehensive dosimetry study. METHODS: We used a dataset consisting of 22 patients undergoing up to 4 cycles of [177Lu]Lu-DOTATATE therapy. MC simulations were used to generate reference absorbed dose maps. In addition, MIRD formalism approaches, namely, single S-value (SSV) and MSV techniques, were performed. A UNEt TRansformer (UNETR) DL architecture was trained using five-fold cross-validation to generate MC-based dose maps. Co-registered CT images were fed into the network as input, whereas the difference between MC and MSV (MC-MSV) was set as output. DL results are then integrated to MSV to revive the MC dose maps. Finally, the dose maps generated by MSV, SSV, and DL were quantitatively compared to the MC reference at both voxel level and organ level (organs at risk and lesions). RESULTS: The DL approach showed slightly better performance (voxel relative absolute error (RAE) = 5.28 ± 1.32) compared to MSV (voxel RAE = 5.54 ± 1.4) and outperformed SSV (voxel RAE = 7.8 ± 3.02). Gamma analysis pass rates were 99.0 ± 1.2%, 98.8 ± 1.3%, and 98.7 ± 1.52% for DL, MSV, and SSV approaches, respectively. The computational time for MC was the highest (~2 days for a single-bed SPECT study) compared to MSV, SSV, and DL, whereas the DL-based approach outperformed the other approaches in terms of time efficiency (3 s for a single-bed SPECT). Organ-wise analysis showed absolute percent errors of 1.44 ± 3.05%, 1.18 ± 2.65%, and 1.15 ± 2.5% for SSV, MSV, and DL approaches, respectively, in lesion-absorbed doses. CONCLUSION: A hybrid transformer-based deep learning model was developed for fast and accurate dose map generation, outperforming the MIRD approaches, specifically in heterogenous regions. The model achieved accuracy close to MC gold standard and has potential for clinical implementation for use on large-scale datasets.

Monte Carlo simulations of organ and effective doses and dose-length product for dental cone-beam CT.

OBJECTIVES: The use of dental cone-beam CT (CBCT) has increased in recent years. We aimed to calculate the organ and effective doses in dental CBCT using Monte Carlo simulation (MCS) and to correlate the effective dose with the dose-length product (DLP), which is a radiation dose index. METHODS: Organ and effective doses were calculated by MCS using the adult male and female reference phantoms of the International Commission on Radiological Protection publication 110 in a half-rotation scan of the CBCT scanner Veraviewepocs 3Df. The simulations were performed by setting nine protocols in combination with the field-of-view (FOV) and imaging region. In addition, DLPs were calculated by MCS using the virtual CT Dose Index (CTDI) and CBCT phantoms, with the same protocol. RESULTS: The effective doses were 55 and 195 µSv at the minimum FOV of Φ40 × H40 mm and maximum FOV of Φ 80 × H80 mm, respectively. The organs with the major contribution to the effective dose were the red bone marrow (11.0‒12.8%), thyroid gland (4.0‒12.7%), salivary gland (21.8‒33.2%), and remaining tissues (35.1‒45.7%). Positive correlations were obtained between the effective dose and calculated DLP using the CTDI and CBCT phantoms. CONCLUSIONS: Organ and effective doses for each protocol of dental CBCT could be estimated using MCS. There was a positive correlation between the effective dose and DLP, suggesting that DLP can be used to estimate the effective dose of CBCT.

Minimum reporting standards should be expected for preclinical radiobiology irradiators and dosimetry in the published literature.

The cornerstones of science advancement are rigor in performing scientific research, reproducibility of research findings and unbiased reporting of design and results of the experiments. For radiation research, this requires rigor in describing experimental details as well as the irradiation protocols for accurate, precise and reproducible dosimetry. Most institutions conducting radiation biology research in in vitro or animal models do not have describe experimental irradiation protocols in sufficient details to allow for balanced review of their publication nor for other investigators to replicate published experiments. The need to increase and improve dosimetry standards, traceability to National Institute of Standards and Technology (NIST) standard beamlines, and to provide dosimetry harmonization within the radiation biology community has been noted for over a decade both within the United States and France. To address this requirement subject matter experts have outlined minimum reporting standards that should be included in published literature for preclinical irradiators and dosimetry.

The ESA Active Dosimeter (EAD) system onboard the International Space Station (ISS).

Ionizing radiation in general and mixed fields of space radiation in particular pose a risk of serious harm to human health. The risk of such adverse effects increases with the duration of the mission, and for all missions outside the protective properties of the Earth's magnetic field and atmosphere. Accordingly, radiation protection is of central importance for all human spaceflight, which is recognized by all international space agencies. To date various systems, analyze and determine the exposure to ionizing radiation within the environment and to the crew onboard the International Space Station (ISS). In addition to this operational monitoring, experiments and technology demonstrations are carried out. This to further enhance systems capabilities, to prepare for exploratory missions, to the Deep Space Gateway and/or to enable for human presence at other celestial bodies. Subsequently the European Space Agency (ESA) decided early to support the development of an active personal dosimeter. Under the auspices of the European Space Research and Technology Center (ESTEC) together with the European Astronaut Center's (EAC) Medical Operations and Space Medicine (HRE-OM) team, a European industrial consortium was formed to develop, build, and test this system. To complete the ESA Active Dosimeter (EAD) Technology Demonstration in space, EAD components were delivered to ISS with the ESA's space missions 'iriss' and 'proxima' in 2015 and 2016. This marked Phase 1 (2015) and 2 (2016-2017) of the EAD Technology Demonstration to which focus is given in this publication. All EAD systems and their functionalities, the different radiation detector, their properties, and calibrations procedures are described. Emphasis is first on the "iriss" mission of September 2015, that provided a complete set of data for an entire space mission from launch to landing, for the first time. Data obtained during Phase 2 in 2016-2017 are discussed thereafter. Measurements with the active radiation detectors of the EAD system provided data of the absorbed dose, dose equivalent, quality factor as well as the various dose contributions during the crossings of the South Atlantic Anomaly (SAA) and/or resulting from galactic cosmic radiation (GCR). Results of the in-flight cross-calibrations among the internal sensors of the EAD systems are discussed and alternative usage of the EAD Mobile Units as area monitors at various different locations inside the ISS is described.

Technical note: High-dose and ultra-high dose rate (UHDR) evaluation of Al2 O3 :C optically stimulated luminescent dosimeter nanoDots and powdered LiF:Mg,Ti thermoluminescent dosimeters for radiation therapy applications.

BACKGROUND: Dosimetry in ultra-high dose rate (UHDR) electron beamlines poses a significant challenge owing to the limited usability of standard dosimeters in high dose and high dose-per-pulse (DPP) applications. PURPOSE: In this study, Al2 O3 :C nanoDot optically stimulated luminescent dosimeters (OSLDs), single-use powder-based LiF:Mg,Ti thermoluminescent dosimeters (TLDs), and Gafchromic EBT3 film were evaluated at extended dose ranges (up to 40 Gy) in conventional dose rate (CONV) and UHDR beamlines to determine their usability for calibration and dose verification in the setting of FLASH radiation therapy. METHODS: OSLDs and TLDs were evaluated against established dose-rate-independent Gafchromic EBT3 film with regard to the potential influence of mean dose rate, instantaneous dose rate, and DPP on signal response. The dosimeters were irradiated at CONV or UHDR conditions on a 9-MeV electron beam. Under UHDR conditions, different settings of pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude were used to characterize the individual dosimeters' response in order to isolate their potential dependencies on dose, dose rate, and DPP. RESULTS: The OSLDs, TLDs, and Gafchromic EBT3 film were found to be suitable at a dose range of up to 40 Gy without any indication of saturation in signal. The response of OSLDs and TLDs in UHDR conditions were found to be independent of mean dose rate (up to 1440 Gy/s), instantaneous dose rate (up to 2 MGy/s), and DPP (up to 7 Gy), with uncertainties on par with nominal values established in CONV beamlines (± 4%). In cross-comparing the response of OSLDs, TLDs and Gafchromic film at dose rates of 0.18-245 Gy/s, the coefficient of variation or relative standard deviation in the measured dose between the three dosimeters (inter-dosimeter comparison) was found to be within 2%. CONCLUSIONS: We demonstrated the dynamic range of OSLDs, TLDs, and Gafchromic film to be suitable up to 40 Gy, and we developed a protocol that can be used to accurately translate the measured signal in each respective dosimeter to dose. OSLDs and powdered TLDs were shown to be viable for dosimetric measurement in UHDR beamlines, providing dose measurements with accuracies on par with Gafchromic EBT3 film and their concurrent use demonstrating a means for redundant dosimetry in UHDR conditions.

Development and validation of the low-cost pregnant female physical phantom for fetal dosimetry in MV photon radiotherapy.

BACKGROUND: Monte Carlo (MC) simulations or measurements in anthropomorphic phantoms are recommended for estimating fetal dose in pregnant patients in radiotherapy. Among the many existing phantoms, there is no commercially available physical phantom representing the entire pregnant woman. PURPOSE: In this study, the development of a low-cost, physical pregnant female phantom was demonstrated using commercially available materials. This phantom is based on the previously published computational phantom. METHODS: Three tissue substitution materials (soft tissue, lung and bone tissue substitution) were developed. To verify Tena's substitution tissue materials, their radiation properties were assessed and compared to ICRP and ICRU materials using MC simulations in MV radiotherapy beams. Validation of the physical phantom was performed by comparing fetal doses obtained by measurements in the phantom with fetal doses obtained by MC simulations in computational phantom, during an MV photon breast radiotherapy treatment. RESULTS: Materials used for building Tena phantom are matched to ICRU materials using physical density, radiation absorption properties and effective atomic number. MC simulations showed that percentage depth doses of Tena and ICRU material comply within 5% for soft and lung tissue, up to 25 cm depth. In the bone tissue, the discrepancy is higher, but again within 5% up to the depth of 5 cm. When the phantom was used for fetal dose measurements in MV photon breast radiotherapy, measured fetal doses complied with fetal doses calculated using MC simulation within 15%. CONCLUSIONS: Physical anthropomorphic phantom of pregnant patient can be manufactured using commercial materials and with low expenses. The files needed for 3D printing are now freely available. This enables further studies and comparison of numerical and physical experiments in diagnostic radiology or radiotherapy.

Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part I - Macroscopic scales.

BACKGROUND: X-ray breast imaging modalities are commonly employed for breast cancer detection, from screening programs to diagnosis. Thus, dosimetry studies are important for quality control and risk estimation since ionizing radiation is used. PURPOSE: To perform multiscale dosimetry assessments for different breast imaging modalities and for a variety of breast sizes and compositions. The first part of our study is focused on macroscopic scales (down to millimeters). METHODS: Nine anthropomorphic breast phantoms with a voxel resolution of 0.5 mm were computationally generated using the BreastPhantom software, representing three breast sizes with three distinct values of volume glandular fraction (VGF) for each size. Four breast imaging modalities were studied: digital mammography (DM), contrast-enhanced digital mammography (CEDM), digital breast tomosynthesis (DBT) and dedicated breast computed tomography (BCT). Additionally, the impact of tissue elemental compositions from two databases were compared. Monte Carlo (MC) simulations were performed with the MC-GPU code to obtain the 3D glandular dose distribution (GDD) for each case considered with the mean glandular dose (MGD) fixed at 4 mGy (to facilitate comparisons). RESULTS: The GDD within the breast is more uniform for CEDM and BCT compared to DM and DBT. For large breasts and high VGF, the ratio between the minimum/maximum glandular dose to MGD is 0.12/4.02 for DM and 0.46/1.77 for BCT; the corresponding results for a small breast and low VGF are 0.35/1.98 (DM) and 0.63/1.42 (BCT). The elemental compositions of skin, adipose and glandular tissue have a considerable impact on the MGD, with variations up to 30% compared to the baseline. The inclusion of tissues other than glandular and adipose within the breast has a minor impact on MGD, with differences below 2%. Variations in the final compressed breast thickness alter the shape of the GDD, with a higher compression resulting in a more uniform GDD. CONCLUSIONS: For a constant MGD, the GDD varies with imaging modality and breast compression. Elemental tissue compositions are an important factor for obtaining MGD values, being a source of systematic uncertainties in MC simulations and, consequently, in breast dosimetry.