Search Results (84)

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor ²²⁵Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized ²²⁵Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care. Full article

Radiopharmaceutical therapy (RPT) offers tumor-selective radiation delivery and represents a promising platform for combination with immune checkpoint inhibitors (ICIs). While prior studies suggest that RPT can stimulate antitumor immunity, synergy with ICIs may depend on radionuclide properties, absorbed dose, and radiation distribution within the tumor microenvironment. This study evaluated how radionuclide selection and dose influence immune stimulation and therapeutic efficacy of GD2-targeted antibody-based RPT combined with ICIs. Dinutuximab, an anti-GD2 monoclonal antibody, was radiolabeled with β⁻-emitters (⁹⁰Y, ¹⁷⁷Lu) or an α-emitter (²²⁵Ac). C57Bl6 mice bearing GD2⁺ tumors received 4 or 15 Gy tumor-absorbed doses, determined by individualized dosimetry, with or without dual ICIs (anti-CTLA-4 and anti-PD-L1). In vivo imaging, ex vivo biodistribution, survival, histological, and gene expression analyses were performed to assess therapeutic and immunological outcomes. All radiolabeled constructs demonstrated preferential uptake in GD2⁺ tumors. Combination therapy improved survival in a radionuclide- and dose-dependent manner, with the greatest benefit in the ²²⁵Ac + ICI group at 15 Gy. Treatment activated type I interferon signaling and increased MHC-I and PD-L1 expression. Notably, ⁹⁰Y reduced regulatory T cells, enhancing CD8⁺/Treg ratios, while ²²⁵Ac induced robust interferon-driven activation. Radionuclide selection and absorbed dose critically shape immune and therapeutic outcomes of antibody-based RPT combined with ICIs, underscoring the importance of delivery mechanism and dose optimization in combination therapy strategies. Full article

Perfluorohexanesulfonamide (PFHxSA) is used as a replacement for legacy PFAS. Non-targeted analysis identified perfluorohexane sulfonic acid (PFHxS) as the primary metabolite of PFHxSA in plasma and liver in a short-term (5-day) repeat dose study with male and female Sprague Dawley rats (Crl:CD(SD)). This evaluation sought to quantitate PFHxSA and PFHxS concentrations by targeted liquid chromatography/mass spectrometry (LC/MS/MS) to further evaluate metabolism and dosimetry following in vivo PFHxSA exposure. In males, quantified plasma and liver PFHxS concentrations were higher than those of its parent, PFHxSA. PFHxS was detected in female plasma and liver at on average 5.3- and 2.9-fold lower, respectively, than PFHxSA. In both sexes, plasma and liver PFHxSA dose concentrations decreased with increasing doses, suggesting hepatic enzyme induction. Liver-to-plasma partitioning favored plasma across all doses in both sexes. In vitro–in vivo extrapolation (IVIVE) suggests higher steady-state plasma concentrations in humans vs. rats for PFHxSA and PFHxS. The in vivo concentrations aligned reasonably (i.e., within 6- to 12.1-fold) with the IVIVE-derived rat plasma estimates. Identifying when PFAS co-exposures may result due to metabolic biotransformation of the parent PFAS to a stable and potentially bioactive metabolite is important to better inform the interpretation of in vivo and in vitro findings. Full article

Background: Quantifying absorbed doses from radiopharmaceuticals within human organs necessitates advanced computational modeling, as direct in vivo measurement remains impractical. Methods: In this study, three Monte Carlo-based simulation codes, Monte Carlo N-Particle version 6 (MCNP6), GEANT4 Application for Tomographic Emission (GATE), and GEANT4-based Architecture for Medicine-Oriented Simulations (GAMOS), were employed to evaluate internal dosimetry following the Medical Internal Radiation Dose (MIRD) formalism. As an illustrative case, simulations were first performed for ^99mTc-MIBI uptake in the myocardium using the anthropomorphic phantom, with the heart modeled as the source organ to assess energy deposition in key target organs. Dose assessments were conducted at two time points: immediately post-injection and at 60 min post-injection (representing the cardiac rest phase), allowing comparison against established clinical reference data. Results: Across all codes, organ-specific dose distributions exhibited strong consistency. The pancreas absorbed the highest dose (GATE: 21%, GAMOS: 20%, MCNP6: 22%), followed by the gallbladder (GATE: 18%, GAMOS: 17%, MCNP6: 18%) and kidneys (GATE: 16%, GAMOS: 15%, MCNP6: 16%). These findings established a consistent organ dose ranking: pancreas > gallbladder > kidneys > spleen > heart/liver, corroborating previously published empirical data. To demonstrate the versatility of the framework, additional simulations were performed with ¹⁸F in an anthropomorphic phantom and with spherical tumor models using therapeutic radionuclides (¹⁷⁷Lu and ²²⁵Ac). This broader application underscores the adaptability of the tri-code approach for both diagnostic and therapeutic scenarios. Conclusions: This comparative analysis highlights the complementary advantages of each Monte Carlo platform. GATE is well-suited for high-fidelity clinical applications where anatomical and physical accuracy are critical. GAMOS proves advantageous for rapid prototyping and iterative modeling workflows. MCNP6 remains a reliable benchmark tool, particularly effective in scenarios requiring robust radiation transport validation. Together, these Monte Carlo frameworks form a validated and adaptable toolkit for advancing internal dosimetry in personalized nuclear medicine, supporting both clinical decision-making and the development of safer, more effective radiopharmaceutical therapies. Full article

Background: FLASH radiotherapy delivers ultra-high dose rates with normal tissue sparing, but mechanisms remain unclear. We present a streamlined workflow for establishing a LINAC-based electron FLASH (eFLASH) platform in low-resource settings without requiring vendor-proprietary hardware or software, or vendor-assisted modifications to broaden accessibility for FLASH studies. Methods: A LINAC was converted to eFLASH with pulse control and monitoring. Automatic frequency control (AFC) was optimized to stabilize dose per pulse (DPP). Beam data were measured with EBT-XD films, and a Monte Carlo (MC) model was commissioned for in vivo dose calculation. We demonstrated in vivo dosimetry in planning studies of mouse whole-brain and rat spinal cord (C1–T2) irradiation. We further assessed the impact of AFC optimization on the FLASH spinal cord study. Results: AFC optimization stabilized DPP at ~0.6 Gy/pulse, reducing large fluctuations under the default setting. MC agreed with measurements within 2% for PDDs and profiles. MC planning showed uniform whole-brain irradiation with 6 MeV FLASH, while the spinal cord study exhibited up to 10% dose fall-off within 1 cm along the cord, suggesting potential dose-volume effects confounding FLASH sparing. Following AFC optimization, 50% of the C1–T2 cord reached >133 Gy/s, a 23% increase versus default. Conclusions: We demonstrated a cost-effective eFLASH platform and verified its accuracy for preclinical studies, expanding the accessibility of FLASH research. Full article

Optical fiber technology is becoming essential in modern radiation therapy, enabling precise, real-time, and minimally invasive monitoring. As oncology moves toward patient-specific treatment, there is growing demand for adaptable and biologically compatible sensing tools. Fiber-optic systems meet this need by integrating into clinical workflows with highly localized dosimetric and spectroscopic feedback. Their small size and flexibility allow deployment within catheters, endoscopes, or treatment applicators, making them suitable for both external beam and internal therapies. This paper reviews the fundamental principles and diverse applications of optical fiber sensing technologies in radiation oncology, focusing on dosimetry, spectroscopy, imaging, and adaptive radiotherapy. Implementations such as scintillating and Bragg grating-based dosimeters demonstrate feasibility for in vivo dose monitoring. Spectroscopic techniques, such as Raman and fluorescence spectroscopy, offer real-time insights into tissue biochemistry, aiding in treatment response assessment and tumor characterization. However, despite such advantages of optical fiber sensors, challenges such as signal attenuation, calibration demands, and limited dynamic range remain. This paper further explores clinical application, technical limitations, and future directions, emphasizing multiplexing capabilities, integration and regulatory considerations, and trends in machine learning development. Collectively, these optical fiber sensing technologies show strong potential to improve the safety, accuracy, and adaptability of radiation therapy in personalized cancer care. Full article

Background: Ferrabis(dicarbollide) ([o-FESAN]⁻) in combination with proton–boron fusion therapy (PBFT) or boron neutron capture therapy (BNCT) are promising alternative radiation modalities for the treatment of breast cancer. The aim of this study was to explore the underlying effects of [o-FESAN]⁻ radio enhancement on breast cancer cells in vitro and in vivo, and to perform comparative dosimetry calculations. Methods: The cellular effects on SKBR-3 and MDA-MB-231 breast cancer cells and MDA-MB-231 xenograft-bearing nude mice induced by carrier-free [o-FESAN]⁻ after BNCT or PBFT were evaluated following recommended protocols. Monte Carlo (MC) dosimetry calculations were performed at the cellular scale for both radiation modalities. Results: Selective retention of [o-FESAN]⁻ within the cytoplasm and nucleus of SKBR-3 and MDA-MB-231 breast cancer cells is demonstrated. Moreover, in vivo studies with MDA-MB-231 xenograft-bearing nude mice show appreciable accumulation of [o-FESAN]⁻ in the tumor. Both radiation modalities induce loss of cellular viability and survival. Comparative dosimetry studies between proton and neutron irradiation agree with the viability data, showing a good correlation between absorbed dose vs. cellular effects. In the case of PBFT, cell structural changes are likely due to necrosis caused by the production of reactive oxygen species (ROS). To explain the radio enhancement effects in more detail, other mechanisms should be taken into consideration. Conclusions: Our results validate the effectiveness of both PBFT and BNCT therapeutic modalities, warranting further studies on carrier-free [o-FESAN]⁻ as a candidate drug for potential clinical translation of radio enhancers in binary radiation therapies. Full article

Background: We present the implementation of an in vivo dosimetry program that enhances treatment setups, ensuring high accuracy that is needed globally. This approach proves valuable in smaller departments by helping to detect and prevent errors. Evaluation studies have shown that in vivo dosimetry is a reliable method for assessing the overall accuracy of treatment delivery. Methods: Comprehensive development and validation of an in vivo dosimetry program using silicon diodes, ionization chambers, and calibrated electrometers for accurate radiation in dose measurements for treatments involving Co-60 or 6 MV X-ray beams. Results: The outcomes demonstrated that all diodes were dependable, with deviations of less than 1% (0.89 ± 0.10 cGy). Calibration curves were generated, showing dose variations of only 0.13% in the diode readings. The overall analysis revealed a mean deviation of up to 1%. Conclusions: These results provide a thorough assessment for patients’ treatment and facilitate timely interventions when needed, helping to ensure that dose variations stay within acceptable limits. Full article

This work presents a Fricke radiochromic gel dosimeter with xylenol orange (XO) and a gelatin matrix modified with sorbitol. The dosimeter, combined with 2D scanning using a flatbed scanner and data processing using dedicated software packages, creates a radiotherapy dosimetry measurement system. The dosimeter reacts to ionizing radiation by changing color as a result of the formation of complexes of Fe³⁺ and XO molecules. It was characterized in terms of thermal and chemical stability and mechanical properties. The presence of sorbitol improved the mechanical and thermal properties of the dosimeter. The dosimeter maintains chemical stability, enabling its use in dosimetric applications, for at least six weeks. The dose–response characteristics of the dosimeter are discussed and indicate a dynamic dose–response of the dosimeter (up to saturation) of about 20 Gy and a linear dose–response of about 12.5 Gy. The following applications of the dosimeter are discussed: (i) as a 2D dosimeter in a plastic container for performing a coincidence test of radiation and mechanical isocenters of a medical accelerator, and (ii) for in vivo dosimetry as a 2D dosimeter alone and simultaneously as a bolus and a 2D dosimeter. Research has shown that the dosimeter has promise in many applications. Full article

Prostate cancer is the second leading cause of cancer-related death in men, with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases representing a critical clinical challenge. Although radium-223 (Ra-223) is approved for treating mCRPC with bone metastases, its efficacy remains limited, necessitating the development of more effective therapies. This study investigates the therapeutic potential of ¹⁷⁷Lu-PSMA-617, a PSMA-targeted radiopharmaceutical, in a murine model of prostate cancer bone metastases. To our knowledge, this is the first study to systematically evaluate ¹⁷⁷Lu-PSMA-617 in an orthotopic bone metastatic prostate cancer model, providing a clinically relevant preclinical platform to assess both imaging and therapeutic performance. We conducted comprehensive preclinical evaluations, including synthesis, stability analysis, cell binding assays, nuclear imaging, in vivo biodistribution, pharmacokinetics, and antitumor efficacy. The synthesis of ¹⁷⁷Lu-PSMA-617 demonstrated high radiochemical yield (99.2%), molar activity (25.5 GBq/μmol), and purity (>98%), indicating high product quality. Stability studies confirmed minimal release of free Lutetium-177, maintaining the compound’s integrity under physiological conditions. In vitro assays showed selective binding and internalization in PSMA-positive LNCaP prostate cancer cells, with negligible uptake in PSMA-negative PC-3 cells. In vivo biodistribution studies demonstrated efficient tumor targeting, with peak uptake in LNCaP tumors (23.31 ± 0.94 %IA/g) at 4 h post-injection. The radiopharmaceutical exhibited favorable pharmacokinetics, with high tumor-to-background ratios (tumor-to-blood, 434.4; tumor-to-muscle, 857.4). Therapeutic efficacy was confirmed by significant survival extension in treated mice (30.7% for 37 MBq and 53.8% for 111 MBq), with median survival times of 34 and 40 days, respectively, compared to 26 days in the control group. Radiation dosimetry analysis indicated a favorable safety profile with a calculated effective dose of 0.127 mSv/MBq. These findings highlight the novelty and translational relevance of using ¹⁷⁷Lu-PSMA-617 in a clinically relevant bone metastasis model, reinforcing its potential as a dual-purpose agent for both targeted therapy and molecular imaging in advanced prostate cancer. Full article

Background/Objectives: Gastrin-releasing peptide receptor is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake of reported GRPR-targeted radioligands limits their clinical applications. Our group previously reported one ⁶⁸Ga-labeled GRPR antagonist, [⁶⁸Ga]Ga-TacsBOMB5 (⁶⁸Ga-DOTA-Pip-[D-Phe⁶,NMe-Gly¹¹,Leu¹³ψThz¹⁴]Bombesin(6–14)), and two agonists, [⁶⁸Ga]Ga-LW01110 (⁶⁸Ga-DOTA-Pip-[D-Phe⁶,Tle¹⁰,NMe-His¹²,Thz¹⁴]Bombesin(6–14)) and [⁶⁸Ga]Ga-LW01142 (⁶⁸Ga-DOTA-Pip-[D-Phe⁶,His⁷,Tle¹⁰,NMe-His¹²,Thz¹⁴]Bombesin(6–14)) showing minimal pancreas uptake. Thus, in this study, we prepared their ¹⁷⁷Lu-labeled analogs, evaluated their therapeutic potentials, and compared them with the clinically evaluated [¹⁷⁷Lu]Lu-AMBA. Methods: GRPR binding affinities were determined by in vitro competition binding assay using PC-3 prostate cancer cells. Longitudinal SPECT/CT imaging and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice. Dosimetry data were calculated from the biodistribution results. Results: The K_i(GRPR) values of Lu-TacsBOMB5, Lu-LW01110, Lu-LW01142, and Lu-AMBA were 12.6 ± 1.02, 3.07 ± 0.15, 2.37 ± 0.28, and 0.33 ± 0.16 nM, respectively. SPECT/CT images and biodistribution results demonstrated good tumor accumulation of [¹⁷⁷Lu]Lu-TacsBOMB5, [¹⁷⁷Lu]Lu-LW01110, and [¹⁷⁷Lu]Lu-LW01142 at early time points with rapid clearance over time. The pancreas uptake of all three [Thz¹⁴]Bombesin(6–14)-derived ligands was significantly lower than that of [¹⁷⁷Lu]Lu-AMBA at all time points. The calculated absorbed doses of [¹⁷⁷Lu]Lu-TacsBOMB5, [¹⁷⁷Lu]Lu-LW01110, and [¹⁷⁷Lu]Lu-LW01142 in PC-3 tumor xenografts were 87.1, 312, and 312 mGy/MBq, respectively, higher than that of [¹⁷⁷Lu]Lu-AMBA (79.1 mGy/MBq), but lower than that of the previously reported [¹⁷⁷Lu]Lu-RM2 (429 mGy/MBq). Conclusions: Our data suggest that [¹⁷⁷Lu]Lu-TacsBOMB5 and [¹⁷⁷Lu]Lu-LW01142 reduce radiation exposure to the pancreas. However, further optimizations are needed for both radioligands to prolong their tumor retention and enhance treatment efficacy. Full article

In vivo dosimetry (IVD) is a vital component of modern radiotherapy, ensuring accurate and safe delivery of radiation doses to patients by measuring dose parameters during treatment. This paper provides a comprehensive overview of IVD, covering its fundamental principles, historical development, and the technologies used in clinical practice. Key techniques, including thermoluminescent dosimeters (TLDs), optically stimulated luminescent dosimeters (OSLDs), diodes, metal-oxide-semiconductor field-effect transistors (MOSFETs), and electronic portal imaging devices (EPIDs), are discussed, highlighting their clinical applications, advantages, and limitations. The role of IVD in external beam radiotherapy, brachytherapy, and pediatric treatments is emphasized, particularly its contributions to quality assurance, treatment validation, and error mitigation. Challenges such as measurement uncertainties, technical constraints, and integration into clinical workflows are explored, along with potential solutions and emerging innovations. The paper also addresses future perspectives, including advancements in artificial intelligence, adaptive radiotherapy, and personalized dosimetry systems. This entry underscores the critical role of IVD in enhancing the precision and reliability of radiotherapy, advocating for ongoing research and technological development. Full article

Objectives: Annexin-A1 is a 37 kDa phospholipid-binding protein which is concentrated in a truncated 34 kDa form (AnnA1) in caveolae on the tumor vascular endothelial cell surface with expression in many tumor types. PRISM developed the monoclonal mouse antibody mAnnA1 against AnnA1 for evaluation of AnnA1 as a potential target for imaging and therapy in oncology. mAnnA1 was humanized to make hAnnA1 for translation to clinical studies. Both PRISM-produced mAnnA1 and cGMP contractor-produced hAnnA1 were investigated using noninvasive PET/CT imaging, and dosimetry was evaluated to enable clinical translation of this strategy and to investigate in vivo behavior of hAnnA1. Methods: Antibodies mAnnA1 and hAnnA1 (PRISM “hAnnA1-P” or contractor generated “hAnnA1-C”) were conjugated with the chelator deferoxamine and evaluated for immunoreactivity with ELISA. Conjugated antibodies were radiolabeled with zirconium-89. Naïve mice, rats, and non-human primates (NHP) were injected with [⁸⁹Zr]mAnnA1 or [⁸⁹Zr]hAnnA1 and imaged with PET/CT up to 10 days post injection. After imaging, mice and rats were euthanized and organs were collected, weighed, and radioactivity was quantified using a gamma counter. Dosimetry in mice and NHPs were calculated using OLINDA. Results: [⁸⁹Zr]mAnnA1 showed similar biodistribution to other antibodies with slow clearance through the liver. Transition to [⁸⁹Zr]hAnnA1-C during the dosimetry studies revealed substantial uptake in the spleen (130 ± 48% ID/g at day 5 post injection in female BALB/c), which was not observed with [⁸⁹Zr]mAnnA1 (5.6 ± 1.7% ID/g at day 7 PI). Further studies in multiple strains of mice showed variable elevated splenic uptake of [⁸⁹Zr]hAnnA1-C across mouse strains, with the highest uptake observed in female BALB/c mice (118.4 ± 23.1% ID/g) and the lowest uptake observed in male CD1 mice (34.7 ± 10.2% ID/g). Additionally, splenic uptake of hAnnA1-C was observed in Fischer rats (2.8 ± 0.6% ID/organ) and NHPs (1.6 ± 0.6% ID/organ), although at lower levels than what was observed in BALB/c mice (8.8 ± 1.8% ID/organ). Dosimetry results showed similar values between estimates based on mouse and NHP data, with the largest difference seen in the spleen (5.2 vs. 2.6 mSv/MBq in females respectively). Sequencing of hAnnA1-C revealed a frameshift mutation in the antibody sequence introduced during cGMP manufacture. Restoration of the antibody sequence by PRISM returned the antibody distribution into alignment with mAnnA1. Conclusions: An aberration introduced during cGMP production of hAnnA1-C resulted in increased splenic uptake and alteration of the biodistribution in mice. PET imaging enabled quantitative detection of the immunogenic behavior of hAnnA1, which led to detection of the sequence error. Restoration of the sequence resulted in an antibody which was non-immunogenic to mice. Full article

Hydrogenated amorphous silicon (a-Si:H) devices on flexible substrates are currently being studied for application in dosimetry and beam flux measurements. The necessity of in vivo dosimetry requires thin devices with maximal transparency and flexibility. For this reason, a thin (<10 µm) a-Si:H device deposited on a thin polyimide sheet is a very valid option for this application. Furthermore, a-Si:H is a material that has an intrinsically high radiation hardness. In order to develop these devices, the HASPIDE (Hydrogenated Amorphous Silicon Pixel Detectors) collaboration has implemented two different device configurations: n-i-p type diodes and charge-selective contact devices.Charge-selective contact-based devices have been studied for solar cell applications and, recently, the above-mentioned collaboration has tested these devices for X-ray dose measurements. In this paper, the HASPIDE collaboration has studied the X-ray and proton response of charge-selective contact devices deposited on Polyimide. The linearity of the photocurrent response to X-ray versus dose-rate has been assessed at various bias voltages. The sensitivity to protons has also been studied at various bias voltages and the wide range linearity has been tested for fluxes in the range from 8.3 × 10⁷ to 2.49 × 10¹⁰ p/(cm² s). Full article

Existing dosimeters for radiation therapy are typically large, and their performance in in vivo system applications has not been assessed. This study develops a compact real-time dosimeter using silicon photomultipliers, plastic scintillators, and optical fibers and evaluates its in vivo applicability for radiation therapy. Dose calibration, dose-rate dependency and linearity, and short-term repeatability tests were conducted using solid water phantoms and bolus materials, and in vivo dosimetry was performed using an in-house phantom. The characterization evaluation results showed high linearity, with a coefficient of determination of 0.9995 for dose rates of 100–600 monitoring units (MU)/min, confirming an error rate within 2% when converted to dosage. In the short-term repeatability tests, the dosimeter exhibited good characteristics, with relative standard deviation (RSD) values lower than 2% for each beam delivery and an RSD value of 0.03% over ten beam deliveries. Dose measurements using the phantom indicated an average error rate of 3.83% compared to the values calculated using the treatment planning system. These results demonstrate a performance comparable to that of commercial metal-oxide-semiconductor field-effect transistors and plastic scintillator-based dosimeters. Based on these findings, the developed dosimeter has significant potential for in vivo radiation therapy applications. Full article