BACKGROUND: In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter 225Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with 225Ac is still open, and 133La features attractive radiation properties to claim this place. However, in order to enable its translation into clinical use, upscaling of the production of this PET radionuclide is needed.
RESULTS: A study on optimal irradiation parameters, separation conditions and an exhaustive product characterization was carried out. In this framework, a proton irradiation of 2 h, 60 µA and 18.7 MeV produced 133La activities of up to 10.7 GBq at end of bombardment. In addition, the performance of four different chromatographic resins were tested and two optimized purification methods presented, taking approximately 20 min with a 133La recovery efficiencies of over 98%, decay corrected. High radionuclide purity and apparent molar activity was proved, of over 99.5% and 120 GBq/µmol, respectively, at end of purification. Furthermore, quantitative complexation of PSMA-617 and mcp-M-PSMA were obtained with molar activities up to 80 GBq/µmol. In addition, both 133La-radioconjugates offered high stability in serum, of over (98.5 ± 0.3)% and (99.20 ± 0.08)%, respectively, for up to 24 h. A first dosimetry estimation was also performed and it was calculated that an 133La application for imaging with between 350 and 750 MBq would only have an effective dose of 2.1-4.4 mSv, which is comparable to that of 18F and 68Ga based radiopharmaceuticals.
CONCLUSIONS: In this article we present an overarching study on 133La production, from the radiation parameters optimization to a clinical dose estimation. Lanthanum-133 activities in the GBq range could be produced, formulated as [133La]LaCl3 with high quality regarding radiolabeling and radionuclide purity. We believe that increasing the 133La availability will further promote the development of radiopharmaceuticals based on macropa or other chelators suitable for 225Ac.

BACKGROUND: The requirement for precise and effective delivery of the actual dose to the patient grows along with the complexity of breast cancer radiotherapy. Dosimetry during treatment has become a crucial component of guaranteeing the efficacy and security.
OBJECTIVE: To propose a dosimetry method during breast cancer radiotherapy based on body surface changes.
METHODS: A total of 29 left breast cancer radiotherapy cases were retroactively retrieved from an earlier database for analysis. Non-rigid image registration and dose recalculation of the planning computed tomography (CT) referring to the Cone-beam computed tomography were performed to obtain dose changes. The study used 3D point cloud feature extraction to characterize body surface changes. Based on the correlation proof, a mapping model is developed between body surface changes and dose changes using neural network framework. The MSE metrics, the Euclidean distances of feature points and the 3D gamma pass rate metric were used to assess the prediction accuracy.
RESULTS: A strong correlation exist between body surface changes and dose changes (first canonical correlation coefficient = 0.950). For the dose deformation field and dose amplitude difference in the test set, the MSE of the predicted and actual values were 0.136 pixels and 0.229 cGy, respectively. After deforming the planning dose into a deformed one, the feature points\' Euclidean distance between it and the recalculated dose changes from 9.267 ± 1.879 mm to 0.456 ± 0.374 mm. The 3D gamma pass rate of 90% or higher for the 2 mm/2% criteria were achieved by 80.8% of all cases, with a minimum pass rate of 75.9% and a maximum pass rate of 99.6%. Pass rate for the 3 mm/2% criteria ranged from 87.8% to 99.8%, with 92.3% of the cases having a pass rate of 90% or higher.
CONCLUSIONS: This study provides a dosimetry method that is non-invasive, real-time, and requires no additional dose for breast cancer radiotherapy.

Image-based dosimetry-guided radiopharmaceutical therapy has the potential to personalize treatment by limiting toxicity to organs at risk and maximizing the therapeutic effect. The 177Lu dosimetry challenge of the Society of Nuclear Medicine and Molecular Imaging consisted of 5 tasks assessing the variability in the dosimetry workflow. The fifth task investigated the variability associated with the last step, dose conversion, of the dosimetry workflow on which this study is based. Methods: Reference variability was assessed by 2 medical physicists using different software, methods, and all possible combinations of input segmentation formats and time points as provided in the challenge. General descriptive statistics for absorbed dose values from the global submissions from participants were calculated, and variability was measured using the quartile coefficient of dispersion. Results: For the liver, which included lesions with high uptake, variabilities of up to 36% were found. The baseline analysis showed a variability of 29% in absorbed dose results for the liver from datasets where lesions included and excluded were grouped, indicating that variation in how lesions in normal liver were treated was a significant source of variability. For other organs and lesions, variability was within 7%, independently of software used except for the local deposition method. Conclusion: The choice of dosimetry method or software had a small contribution to the overall variability of dose estimates.

OBJECTIVE: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.
METHODS: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated.
RESULTS: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs.
CONCLUSIONS: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.

OBJECTIVE: Radiation doses to adult patients submitted to cerebral angiography and intracranial aneurysms treatments were assessed by using DICOM Radiation Dose Structured Reports (RDSR) and Monte Carlo simulations. Conversion factors to estimate effective and organ doses from Kerma-Area Product (PKA) values were determined.
METHODS: 77 cerebral procedures performed with five angiographic equipment installed in three Italian centres were analyzed. Local settings and acquisition protocols were considered. The geometrical, technical and dosimetric data of 16,244 irradiation events (13305 fluoroscopy, 2811 digital subtraction angiography, 128 cone-beam CT) were extracted from RDSRs by local dose monitoring systems and were input in MonteCarlo PCXMC software to calculate effective and organ doses. Finally, conversion factors to determine effective and organ doses from PKA were determined. Differences between centres were assessed through statistical analysis and accuracy of dose calculation method based on conversion factors was assessed through Bland-Altman analysis.
RESULTS: Large variations in PKA (14-561 Gycm2) and effective dose (1.2-73.5 mSv) were observed due to different degrees of complexity in the procedures and angiographic system technology. The most exposed organs were brain, salivary glands, oral mucosa, thyroid and skeleton. The study highlights the importance of recent technology in reducing patient exposure (about fourfold, even more in DSA). No statistically significant difference was observed in conversion factors between centres, except for some organs. A conversion factor of 0.09 ± 0.02 mSv/Gycm2 was obtained for effective dose.
CONCLUSIONS: Organ and effective doses were assessed for neuro-interventional procedures. Conversion factors for calculating effective and organ doses from PKA were provided.

UNASSIGNED: To evaluate intrafractional motion effects as a function of peak-to-peak motion and period during single-field, single-fraction and single-field, multifraction irradiation of the moving target in spot-scanning proton therapy.
UNASSIGNED: An in-house dynamic phantom was used to simulate peak-to-peak motion of 5, 10, and 20 mm with periods of 2, 4, and 8 seconds. The dose distribution in the moving target was measured using radiochromic films. During the perpendicular motion, the film was fixed and moved perpendicular to the beam direction without changing the water equivalent thickness (WET). During longitudinal motion, the film was fixed and moved along the beam direction, causing a change in WET. Gamma index analysis was used with criteria of 3%/3 mm and 3%/2 mm to analyze the dose distributions.
UNASSIGNED: For single-fraction irradiation, varying the period did not result in a significant difference in any of the metrics used (P > .05), except for the local dose within the planning target volume (P < .001). In contrast, varying peak-to-peak motion was significant (P < .001) for all metrics except for the mean planning target volume dose (P ≈ .88) and the local dose (P ≈ .47). The perpendicular motion caused a greater decrease in gamma passing rate (3%/3 mm) than WET variations (65% ± 5% vs 85% ± 4%) at 20 mm peak-to-peak motion.
UNASSIGNED: The implementation of multifraction irradiation allowed to reduce hot and cold spots but did not reduce dose blurring. The motion threshold varied from 7 to 11 mm and depended on the number of fractions, the type of motion, the acceptance criteria, and the calculation method used.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients\' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients\' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients\' toxicity and dosimetric analyses.

The kV cone beam computed tomography (CBCT) is one of the most common imaging modalities used for image-guided radiation therapy (IGRT) procedures. Additional doses are delivered to patients, thus assessment and optimization of the imaging doses should be taken into consideration. This study aimed to investigate the influence of using fixed and patient-specific FOVs on the patient dose. Monte Carlo simulations were performed to simulate kV beams of the imaging system integrated into Truebeam linear accelerator using BEAMnrc code. Organ and size-specific effective doses resulting from chest and pelvis scanning protocols were estimated with DOSXYZnrc code using a phantom library developed by the National Cancer Institute (NCI) of the US. The library contains 193 (100 male and 93 female) mesh-type computational human adult phantoms, and it covers a large ratio of patient sizes with heights and weights ranging from 150 to 190 cm and 40 to 125 kg. The imaging doses were assessed using variable FOV of three sizes, small (S), medium (M), and large (L) for each scan region. The results show that the FOV and the patient size played a major role in the scan dose. The average percentage differences (PDs) for doses of organs that were fully inside the different FOVs were relatively low, all within 11% for both protocols. However, doses to organs that were scanned partially or near the FOVs were affected significantly. For the chest protocol, the inclusion of the thyroid in the scan field could give a dose of 1-7 mGy/100 mAs to the thyroid, compared to 0.4-1 mGy/100 mAs when it was excluded. Similarly, on average, testes doses could be 6 mGy/100 mAs for the male pelvis protocol compared to 3 mGy/100 mAs when it did not lie in the field irradiated. These dose differences resulted in an average increase of up to 27% in the size-specific effective dose of the protocols. Since changing the field size is possible for CBCT scans, the results suggest that patient-specific scanning protocols could be applied for each scan area in a manner similar to that used for CT scans. Adjustment of the FOV size should be subject to the clinical needs, and assist in improving the treatment accuracy. The patient\'s height and weight might be considered as the main factors upon which, the selection of the appropriate patient-specific protocol is based. This approach should optimize the imaging doses used for IGRT procedures by minimizing doses of a large ratio of patients.

OBJECTIVE: This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients.
METHODS: The study cohort consisted of 90 patients from the Fudan University Shanghai Cancer Center and 59 patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. A total of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value.
RESULTS: The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong p < 0.05).
CONCLUSIONS: Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients.
CONCLUSIONS: Integrating DL-derived features with dose-volume metrics provides a promising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.

OBJECTIVE: To assess the impact of changes in sinus aeration on dose variation in nasopharyngeal cases using a single beam with various field sizes and real patient computed tomography (CT) images.
METHODS: The calculations were carried out on a computer equipped with an Intel Xeon (R) Gold 5118 processor operating at 2.30 GHz in 2022 at Taibah University, Al Madinah Al Munawwarah for a retrospective nasopharyngeal case. At the patient level, the impact on dose distribution was examined for different field sizes by comparing the percentage depth dose. The dose discrepancy was evaluated by comparing the dose delivered without considering the anatomical changes observed in the initial fraction to the dose adjusted to account for these changes using a 2D gamma analysis. With a criterion of 1% dose difference and 1 mm distance to agreement, the gamma level for analysis was set at 95%.
RESULTS: The study findings indicated that the observed effect diminished by approximately 50% for both 5 cm x 5 cm and 10 cm x 10 cm field sizes compared to the 3 cm x 3 cm size, where there was an overlap between the planning target volume and sinusitis.
CONCLUSIONS: The study concluded that the impact of dose discrepancy was more pronounced in smaller field sizes.