Absorbed Organ Doses Research Articles

EFFECTIVE DOSE ANALYSIS IN ABDOMEN AP EXAMINATION PATIENTS WITH CALDOSE_X VERSION 5.0

This study evaluates radiation dose exposure during diagnostic radiology procedures using X-rays and their potential risks, including cancer, to optimize radiation safety through the CALDose_X software that calculates the absorbed organ dose, effective dose, and cancer risk, according to the lowest possible achievable (ALARA) principle. This study used a quantitative experimental design to evaluate the impact of filter thickness variations on Entrance Surface Air Kerma (ESAK) and effective dose by analyzing data from 54 patients undergoing AP Abdominal X-ray examinations. The results showed that the effective dose to the abdominal organs varied with exposure factors and Focus to Detector Distance (FDD), where the colon wall had the highest sensitivity with doses ranging from 0.030 mSv to 0.126 mSv, followed by the stomach and pancreas. Increasing kV, mAs, and FDD increased the effective dose, emphasizing the importance of careful dose management. This study concluded that exposure factors and FDD affect the effective dose received by the abdominal organs, with recommendations to monitor patient doses, revise national diagnostic reference levels, and establish standard protocols with health authorities. Keywords: CALDose_X, X-ray Exposure Factor, patient dose, ESAK, Effective Dose, Abdomen AP.

Estimation of organ-absorbed doses in patients undergoing chest and abdominal X-ray examinations using Monte Carlo-based software

Estimation of organ-absorbed doses in patients undergoing chest and abdominal X-ray examinations using Monte Carlo-based software

Dose response analysis of protracted absorbed organ dose and site-specific cancer incidence in Sweden after the Chernobyl accident

Dose response analysis of protracted absorbed organ dose and site-specific cancer incidence in Sweden after the Chernobyl accident

Biodistribution and Radiation Dosimetry for 68 Ga-DOTA-CCK-66, a Novel CCK 2 R-Targeting Compound for Imaging of Medullary Thyroid Cancer.

Cholecystokinin 2 receptor (CCK 2 R) is a promising target for imaging and treatment of medullary thyroid cancer due to its overexpression in over 90% of tumor cells. 68 Ga-DOTA-CCK-66 is a recently introduced PET tracer selective for CCK 2 R, which has shown favorable pharmacokinetics in vivo in preclinical experiments. In order to further investigate safety and suitability of this tracer in the human setting, whole-body distribution and radiation dosimetry were evaluated. Six patients with a history of medullary thyroid cancer were injected intravenously with 169 ± 19 MBq of 68 Ga-DOTA-CCK-66. Whole-body PET/CT scans were acquired at 10 minutes, 1 hour, 2 hours, and 4 hours after tracer injection. Time-activity curves per organ were determined, and mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Injection of a standard activity of 150 MBq of 68 Ga-DOTA-CCK-66 results in an effective dose of 4.5 ± 0.9 mSv. The highest absorbed organ doses were observed in the urinary bladder wall (40 mGy) and the stomach (15 mGy), followed by the kidneys (6 mGy), as well as the liver and the spleen (3 mGy each). CCK 2 R-expressing tumor manifestations could be detected in 2 of the 6 patients, including lymph node, bone, and liver metastases. 68 Ga-DOTA-CCK-66 exhibits a favorable dosimetry. Beyond physiologic receptor expression of the stomach, no other relevant tracer accumulation could be observed, rendering this organ at risk in case of subsequent radioligand therapy using 177 Lu-DOTA-CCK-66.

Comparison of the tolerability of 161Tb- and 177Lu-labeled somatostatin analogues in the preclinical setting.

[177Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [177Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [161Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of 161Tb- and 177Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice. Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the 177Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study. The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161Tb- and 177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities. Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [161Tb]Tb-DOTA-LM3 and [161Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective 177Lu-based analogues.

Dosimetry of lutetium-177-PSMA-I&amp;T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&amp;T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&amp;T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&amp;T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&amp;T injection at cycle 1. Tumors &gt;1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&amp;T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

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

BackgroundTau 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.ResultsFrom 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%.ConclusionsThe 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 registrationRetrospectively Registered at Clinicaltrials.gov (NCT03625128) on 12 July, 2018, https://clinicaltrials.gov/study/NCT03625128.

Biodistribution and radiation dosimetry of 124I-mIBG in adult patients with neural crest tumours and extrapolation to paediatric models

AimPositron emission tomography (PET) using 124I-mIBG has been established for imaging and pretherapeutic dosimetry. Here, we report the first systematic analysis of the biodistribution and radiation dosimetry of 124I-mIBG in patients with neural crest tumours and project the results to paediatric patient models.MethodsAdult patients with neural crest tumours who underwent sequential 124I-mIBG PET were included in this retrospective single-center analysis. PET data were acquired 4, 24, 48, and/or 120 h after administration of a mean of 43 MBq 124I-mIBG. Whole-body counting and blood sampling were performed at 2, 4, 24, 48 and 120 h after administration. Absorbed organ dose and effective dose coefficients were estimated in OLINDA/EXM 2.2 according to the MIRD formalism. Extrapolation to paediatric models was performed based on mass-fraction scaling of the organ-specific residence times. Biodistribution data for adults were also projected to 123I-mIBG and 131I-mIBG.ResultsTwenty-one patients (11 females, 10 males) were evaluated. For adults, the organs exposed to the highest dose per unit administered activity were urinary bladder (1.54 ± 0.40 mGy/MBq), salivary glands (0.77 ± 0.28 mGy/MBq) and liver (0.65 ± 0.22 mGy/MBq). Mean effective dose coefficient for adults was 0.25 ± 0.04 mSv/MBq (male: 0.24 ± 0.03 mSv/MBq, female: 0.26 ± 0.06 mSv/MBq), and increased gradually to 0.29, 0.44, 0.69, 1.21, and 2.94 mSv/MBq for the 15-, 10-, 5-, 1-years-old, and newborn paediatric reference patients. Projected mean effective dose coefficients for 123I-mIBG and 131I-mIBG for adults were 0.014 ± 0.002 mSv/MBq and 0.18 ± 0.04 mSv/MBq, respectively.ConclusionPET-based derived radiation dosimetry data for 124I-mIBG from this study agreed well with historical projected data from ICRP 53. The effective dose coefficients presented here may aid in guidance for establishing weight-based activity administration protocols.

The effect of optimum, indication-specific imaging fields on the radiation exposure from CBCT examinations of impacted maxillary canines and mandibular third molars

Objective Indication-specific optimum field-of-views (FOVs) have been assessed for CBCT scans of impacted maxillary canines and mandibular third molars, as 40∅ × 35 mm and 35∅ × 35 mm, respectively. The objective was to investigate possible changes in absorbed organs and effective doses, for these two imaging indications, performing CBCT examinations with optimum FOV sizes instead of commonly used FOVs. Additionally, radiation exposure-induced cancer risk was calculated for both imaging indications with optimum FOVs. Methods An adult female head phantom (ATOM 702-D, CIRS, Norfolk, VA, USA) was scanned using Planmeca Viso G7 CBCT-device (Planmeca, Helsinki, Finland). Scanning factors, different FOV sizes, dose-area product (DAP) values and anatomical FOV locations were used for Monte Carlo PCXMC-simulation and ImpactMC software. In the PCXMC- simulation, 10-year-old child and 30-year-old adult phantoms were used to estimating effective and absorbed organ doses. Results The effective dose varied from 58 µSv to 284 µSv for impacted maxillary canines, and from 38 µSv to 122 µSv for mandibular third molars, the lowest dose value for each corresponding to optimum FOV. Effective dose reduction between the optimum FOV and the smallest common FOV of 50∅ × 50 mm, maintaining other scanning factors constant, was 33% for impacted maxillary canines, and 45% for mandibular third molars. At all examinations, the highest absorbed organ doses were in salivary glands or in oral mucosa. Conclusions Optimum FOVs, 40∅ × 35 mm for impacted maxillary canine and 35∅ × 35 mm for mandibular third molar, could decrease effective doses received by young patients, and improve radiation safety in these common CBCT imaging procedures.

Dose-response analysis of protracted absorbed organ dose and site-specific cancer incidence in Sweden after the Chernobyl nuclear power plant accident.

Adult males in Sweden exhibit an increased risk of cancer associated with an increased absorbed dose to the colon from the Chernobyl accident. A closed cohort, with information on hunter status, included all individuals living in northern Sweden in 1986. Complete annual information on exposure to 137Cs at the dwelling coordinate was available for a total of 2,104,101 individuals. A nested case-control method with four controls matched for year of cancer diagnosis and year of birth, was used. Individual absorbed organ doses were calculated between 1986 and 2020 including external and internal exposure. Hazard ratios (HR) per mGy with 95% confidence intervals (95% CI) were calculated using conditional logistic regression adjusted for rural/nonrural habitat, education level and pre-Chernobyl cancer incidence 1980 to 1985. A total of 161,325 cancer cases in males and 144,439 in females were included. The adjusted HR per mGy for all cancer sites combined was 1.027 (95% CI = 1.022, 1.031) in males and 1.011 (95% CI = 1.006, 1.017) in females. In a post hoc analysis accounting for both remaining confounding from hunter lifestyle and the pre-Chernobyl cancer incidence by county, the adjusted HR per mGy for all cancer sites combined was 1.014 (95% CI = 1.009, 1.019) in males and 1.000 (95% CI = 0.994, 1.006) in females. The post hoc analysis suggested an increased risk of cancer in the colon, pancreas, and stomach, respectively, in males, and lymphoma in females. Increased cancer risk estimates were found for some specific cancer sites but remaining uncontrolled confounding due to hunter lifestyle could not be ruled out.

Clinical Characterization of [18F]T-008, a Cholesterol 24-Hydroxylase PET Ligand: Dosimetry, Kinetic Modeling, Variability, and Soticlestat Occupancy.

This series of studies characterized [18F]T-008, a PET radiotracer for imaging cholesterol 24-hydroxylase (CH24H), in healthy volunteers (ClinicalTrials.gov identifier NCT02497235). Assessments included radiation dosimetry, kinetic modeling, test-retest variability (TRT) evaluation, and a dose occupancy evaluation using soticlestat, a selective CH24H inhibitor. Soticlestat is currently in phase 3 development for the treatment of seizures in Dravet syndrome and Lennox-Gastaut syndrome. Methods: In the dosimetry study, 5 participants (3 men) underwent serial whole-body scans to estimate organ-absorbed doses and effective doses of [18F]T-008 using OLINDA/EXM 1.1. For the kinetic modeling and TRT study, 6 participants (all men) underwent two 210-min dynamic [18F]T-008 PET scans with arterial blood sampling. The regional total volume of distribution was estimated using a 1-tissue-compartment model, a 2-tissue-compartment model, and Logan graphic analysis. In the dose occupancy study, 11 participants (all men) underwent 120-min scans at baseline and 2 time points (peak and trough) after receiving single oral doses of soticlestat (50-600 mg). The relationship between effect-site soticlestat concentration and brain occupancy was evaluated with a specially developed pharmacokinetic model and a saturable maximal occupancy model. Results: The estimated mean whole-body effective dose was 0.0292 mSv/MBq (SD, 0.00147 mSv/MBq). [18F]T-008 entered the brain rapidly, with a distribution consistent with known CH24H distribution densities. The 2-tissue-compartment model and Logan graphic analysis best described the tracer kinetics. The mean TRT for estimating total volume of distribution was 7%-15%. Single doses of soticlestat in the range 50-600 mg resulted in occupancies of 64%-96% at 2 h and 11%-79% at 24 h. The estimated half-maximal effect-site concentration of soticlestat was 5.52 ng/mL. Conclusion: [18F]T-008 is a suitable PET radiotracer for quantitatively analyzing CH24H in the human brain. Using [18F]T-008 and PET, we demonstrated that soticlestat was brain-penetrant and established target engagement by displacing [18F]T-008 in a dose-dependent manner in the brain.

Radiation dose evaluation to organs in neonatal patients by field size during potable X-ray examination in incubators: A Monte Carlo simulation study.

Neonatal patients located in incubators are exposed to as many as 159 radiographs until discharge. To reduce the dose exposed to the patient, factors that may cause unnecessary exposure to the patient were judged. When conducting portable X-rays of neonatal patients located in an incubator, it is not easy to determine the exact field size because collimation light is exposed on the acrylic plate, an incubator canopy, and the resulting shadow is reflected on the patient's body. This study aims to measure the organ dose exposed to the patient according to the field size when a portable radiograph is given to a neonatal patient in a neonatal intensive care unit (NICU) incubator. To identify the absorbed organ dose depending on the radiation field size during portable X-ray examination of neonatal patient, a Monte Carlo N-Particle (MCNP) simulation, a SpeckCalc program, and a neonatal phantom from the ICRP 89 are applied for the calculation. According to the minimal field size (MinFS) standards of the European Commission (EC), the smaller field size is intended to measure tightly from the top of the lung apices to the bottom of the genitals; a larger field size is also calculated by adding 6 cm in width and length. Compared to the hospital C condition from the previous study, the larger and smaller field sizes are decreased by an average of 45% and 67%, respectively. Study results also show a 42% reduction in smaller field size compared to the larger field size. When taking chest and abdomen radiographic images of neonatal patients in incubators, appropriate field sizes are required to prevent inappropriate dose absorption for non-thoracic organs.

A personalized Monte Carlo study of tumor and critical organ doses for Trans-arterial Radioembolization patients.

Trans-arterial Radioembolization (TARE) is an intra-arterial treatment method for liver malignancies. In this procedure, the therapeutic tumor dose is significant for predicting the treatment effectiveness while the dose absorbed in an organ at risk provides an understanding of its tolerance to radiation. This study proposes a Monte Carlo (MC) approach for determining absorbed organ doses for patients undergoing TARE treatment. The technique is based on the use of a voxel-based partial body model generated for each patient from his/her anatomical image data to represent the critical body structures more realistically. These structures are first segmented from image slices to create an image block which is then incorporated into a radiation transport package (MCNP6.2) to perform MC simulations. When used along with the parameters specific to a patient's treatment, such as lung-shunt factor (LSF), tumor-to-normal liver ratio (TLR), fractional uptakes, and administered activity, this approach allowed more accurate simulation of radiation interactions and hence provided absorbed doses specific to a TARE patient. The MC method also calculated the absorbed doses in organs or tissues that were close to target tissues for which the MIRD formalism makes no predictions. MIRD calculations were found to overestimate the absorbed doses by as much as 11% in lungs, 5% in liver, and 20% in tumor volumes. This raises concerns about the treatment's efficacy when estimating the correct activity to be administered to a patient. When each patient simulation was repeated with a 90Y source spectrum to reflect the distribution of varying beta energies, the liver and the lungs were observed to receive relatively lower doses than those obtained with monoenergetic beta particles. Thus, it can be stated that the approach adopted in this study offers a more precise model of the patient's critical tissues and serves as a personalized dosimetric tool for TARE treatment planning.

Comparative in vivo biodistribution of cells labelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS using PET

BackgroundIn vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[89Zr]Zr-(oxinate)4 and [89Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq).ResultsThe biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [89Zr]Zr-(oxinate)4 labelled cells migrated to the liver, while the signal from [89Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [89Zr]Zr-(oxinate)4 labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [89Zr]Zr-DFO-NCS labelled cells, whereas [89Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [89Zr]Zr-(oxinate)4 labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [89Zr]Zr-DFO-NCS compared to [89Zr]Zr-(oxinate)4, for both cell types. Although the bone uptake was higher for [89Zr]Zr-(oxinate)4 labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose.ConclusionThe [89Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [89Zr]Zr-(oxinate)4 suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [89Zr]Zr-DFO-NCS labelled cell.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Optimization of Radiolabeling of a [90Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation.

For patients with acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. In addition to standard conditioning regimens for HCT, high-dose radioimmunotherapy (RIT) offers the unique opportunity to selectively deliver a high dose of radiation to the bone marrow while limiting side effects. Modification of a CD66b-specific monoclonal antibody (mAb) with a DTPA-based chelating agent should improve the absorbed dose distribution during therapy. The stability and radioimmunoreactive fraction of the radiolabeled mAbs were determined. Before RIT, all patients underwent dosimetry to determine absorbed doses to bone marrow, kidneys, liver, and spleen. Scans were performed twenty-four hours after therapy for quality control. A radiochemical purity of >95% and acceptable radioimmunoreactivity was achieved. Absorbed organ doses for the liver and kidney were consequently improved compared to reported historical data. All patients tolerated RIT well with no treatment-related acute adverse events. Complete remission could be observed in 4/5 of the patients 3 months after RIT. Two patients developed delayed liver failure unrelated to the radioimmunotherapy. The improved conjugation and radiolabeling procedure resulted in excellent stability, radiochemical purity, and CD66-specific radioimmunoreactivity of 90Y-labeled anti-CD66 mAb. RIT followed by conditioning and HCT was well tolerated. Based on these promising initial data, further prospective studies of [90Y]Y-DTPA-Bn-CHX-A″-anti-CD66-mAb-assisted conditioning in HCT are warranted.

18F]FNDP PET neuroimaging test-retest repeatability and whole-body dosimetry in humans.

Soluble epoxide hydrolase (sEH) is an enzyme that shapes immune signaling through its role in maintaining the homeostasis of polyunsaturated fatty acids and their related byproducts. [18F]FNDP is a radiotracer developed for use with positron emission tomography (PET) to image sEH, which has been applied to imaging sEH in the brains of healthy individuals. Here, we report the test-retest repeatability of [18F]FNDP brain PET binding and [18F]FNDP whole-body dosimetry in healthy individuals. Seven healthy adults (4 men, 3 women, ages 40.1 ± 4.6years) completed [18F]FNDP brain PET on two occasions within a period of 14days in a test-retest study design. [18F]FNDP regional total distribution volume (VT) values were derived from modeling time-activity data with a metabolite-corrected arterial input function. Test-retest variability, mean absolute deviation, and intraclass correlation coefficient (ICC) were investigated. Six other healthy adults (3 men, 3 women, ages 46.0 ± 7.0years) underwent [18F]FNDP PET/CT for whole-body dosimetry, which was acquired over 4.5h, starting immediately after radiotracer administration. Organ-absorbed doses and the effective dose were then estimated. The mean test-retest difference in regional VT (ΔVT) was 0.82 ± 5.17%. The mean absolute difference in regional VT was 4.01 ± 3.33%. The ICC across different brain regions ranged from 0.92 to 0.99. The organs with the greatest radiation-absorbed doses included the gallbladder (0.081 ± 0.024mSv/MBq), followed by liver (0.077 ± 0.018mSv/MBq) and kidneys (0.063 ± 0.006mSv/MBq). The effective dose was 0.020 ± 0.003mSv/MBq. These data support a favorable test-retest repeatability of [18F]FNDP brain PET regional VT. The radiation dose to humans from each [18F]FNDP PET scan is similar to that of other 18F-based PET radiotracers.

Radiation exposure in cone beam CT measured using a MOSFET and RPLGD dosimeter and Monte Carlo simulation in phantom.

Due to the wide application of the cone beam computed tomography (CBCT) in clinical practice, it is important to assess radiation dose of CBCT more accurately and efficiently in different clinical applications. This study aims to calculate effective and absorbed doses in CBCT measured in an anthropomorphic phantom using computer-based Monte Carlo (PCXMC) software, and to conduct comparative evaluations of MOSFET (metal- oxide- semiconductor field-effect transistor) and radiophotoluminescence glass dosimeters (RPLGD). Effective and absorbed organ doses are compared with those obtained using MOSFET and RPLGD dosimetry in an anthropomorphic phantom given the same exposure settings. Effective and absorbed organ doses from CBCT during scout and main projections are calculated using PCXMC and PCXMCRotation software, respectively. The mean effective dose from CBCT calculated using PCXMC software is 233.8μSv, while the doses calculated using dosimetry (MOSFET and RPLGD) are 266.67μSv and 268.78μSv, respectively. The X-ray source variation is 0.79%. The prescription limits based on the Friedman test for MOSFET and RPLGD pre-points (i.e., in an analytical analysis of diagnostic names in CBCT) are not statistically significant. The calculated correlation coefficient between MOSFET- and RPLGD-derived absorbed dose values with respect to a field of view CBCT parameter of 17×13.5 mm is r = 0.8623. The study demonstrates that the PCXMC software may be used as an alternative to MOSFET and RPLGD dosimetry for effective and absorbed organ dose estimation in CBCT conducted with a large FOV in an anthropomorphic phantom.

Prediction of absorption dose of radiation on Thorax CT imaging in geriatric patients with COVID-19 by classification algorithms

Objective: The aim of the study is to predict the absorbed radiation dose on thorax CT imaging in geriatric patients with COVID-19. Materials and Method: The SIEMENS SENSATION 64 CT scanner was performed with real protocols to patients (male/female phantom) using Monte Carlo simulation methods with the patient’s real height and weight nts and the actual parameters CT scanner. Absorbed organ doses have been calculated based on these Monte Carlo results. These results were used to predict the optimal absorbed radiation dose by Artificial Neural Network, Linear Discriminant Analysis, Random Forest Classification, and Naive-Bayes Classification algorithms. The dose values were clustered for genders by the Fuzzy C-Means algorithm. Results: The ages of the patients were between 60 and 70 years. The Body Mass Indexes of male and female patients were 26.11 ± 4.49 and 25.03 ± 4.86 kg/m2 respectively. All classification algorithms were validated with approximately 100% success. The Fuzzy C-Means technique was found to be successful in clustering the dose values for gender clusters. Conclusion: While the predicted and the observed values of patients do not change in the organs/tissues around and outside of the thorax, they generally vary in the intra-thoracic organs and tissues. It can be concluded that data-driven techniques are useful to obtain optimal radiation doses for organs/tissues in CT imaging.