Dosimetry Analysis Research Articles

Single Chelator-Minibody Theranostic Agents for 89Zr PET Imaging and 177Lu Radiopharmaceutical Therapy of PSMA-Expressing Prostate Cancer.

Here we describe an anti-prostate-specific membrane antigen (PSMA) minibody (IAB2MA) conjugated to an octadentate, macrocyclic chelator based on four 1-hydroxypyridin-2-one coordinating units (Lumi804 [L804]) labeled with 89Zr (PET imaging) and 177Lu (radiopharmaceutical therapy), with the goal of developing safer and more efficacious treatment options for prostate cancer. Methods: L804 was compared with the current gold standard chelators, DOTA and deferoxamine (DFO), conjugated to IAB2MA for radiolabeling with 177Lu and 89Zr in cell binding, preclinical biodistribution, imaging, dosimetry, and efficacy studies in the PSMA-positive PC3-PIP tumor-bearing mouse model of prostate cancer. Results: Quantitative radiolabeling (>99% radiochemical yield) of L804-IAB2MA with 177Lu or 89Zr was achieved at ambient temperature in under 30 min, comparable to 89Zr labeling of DFO-IAB2MA. In contrast, DOTA-IAB2MA was radiolabeled with 177Lu for 30 min at 37°C in approximately 90% radiochemical yield, requiring further purification. Using europium(III) as a luminescent surrogate, high binding affinity of Eu-L804-IAB2MA to PSMA was demonstrated in PC3-PIP cells (dissociation constant, 4.6 ± 0.6 nM). All 4 radiolabeled constructs showed significantly higher levels of internalization after 30 min in the PC3-PIP cells than in PSMA-negative PC3-FLU cells. The accumulation of 177Lu- and 89Zr-L804-IAB2MA in PC3-PIP tumors and all organs examined (i.e., heart, liver, spleen, kidney, muscle, salivary glands, lacrimal glands, carcass, and bone) was significantly lower than that of 177Lu-DOTA-IAB2MA and 89Zr-DFO-IAB2MA at 96 and 72 h after injection, respectively. Generally, SPECT/CT and PET/CT imaging data showed no significant difference in the SUVmean of the tumors or muscle between the radiotracers. Dosimetry analysis via both organ-level and voxel-level dose calculation methods indicated significantly higher absorbed doses of 177Lu-DOTA-IAB2MA in tumors, kidney, liver, muscle, and spleen than of 177Lu-L804-IAB2MA. PC3-PIP tumor-bearing mice treated with single doses of 177Lu-L804-IAB2MA (18.4 or 22.2 MBq) exhibited significantly prolonged survival and reduced tumor volume compared with unlabeled minibody control. No significant difference in survival was observed between groups of mice treated with 177Lu-L804-IAB2MA or 177Lu-DOTA-IAB2MA (18.4 or 22.2 MBq). Treatment with 177Lu-L804-IAB2MA resulted in lower absorbed doses in tumors and less toxicity than that of 177Lu-DOTA-IAB2MA. Conclusion: 89Zr- and 177Lu-L804-IAB2MA may be a promising theranostic pair for imaging and therapy of prostate cancer.

Dosimetric Analyses of the Three Radiation Techniques Used in the EORTC 22922/10925 IM-MS Breast Cancer Trial

PurposeThe aim of the current study is to compare the dosimetry of 3 radiation therapy (RT) techniques used in the EORTC 22922/10925 trial for irradiating the internal mammary (IM) and medial supraclavicular nodes (MS) using a treatment planning system available nowadays for dose calculation. MethodsWe performed a retrospective dosimetry analysis of anonymised data; thus, ethics approval was not required. Ten cases of left-sided breast were randomly selected for RT planning to a total dose of 50 Gy in 25 fractions. The treatment planning was done according to the trial's protocol and under the supervision of the EORTC trial's coordinators. Doses to planning target volumes (PTV) and to organs at risk (OARs) are reported. Data is presented in descriptive statistics. ResultsA total of 10 cases and 40 treatment plans (4 plans per case: standard-plan A, modified standard-plan B, individualised-plan C and breast-only–plan D). For all planning techniques, the mean dose to the PTV of the left breast (plan A-D) and the PTV-MS (plan A-C) exceeded 95% of the prescribed dose (>47.5 Gy). The individualised technique (plan C) had a lower coverage for PTV-IM, with a mean of 87% of the prescribed dose compared to ∼102% for plans A and B. The dose to OARs varied between techniques, with the mean heart dose being higher in the standard and modified standard techniques (18.3 and 16.6 Gy, respectively) compared to the individualised technique (9.5 Gy). ConclusionsThe 3 RT techniques used in the trial varied in target coverage and OARs dose. Our results may help to understand the observed larger absolute benefit of individualised IM-MS treatment planning in terms of breast cancer outcomes.

152 Dosimetry Analysis of OAR in HDR IBT Treatment for Liver Malignancy with Iridium-192 Source

152 Dosimetry Analysis of OAR in HDR IBT Treatment for Liver Malignancy with Iridium-192 Source

A comprehensive dosimetry analysis of barakah nuclear power plant: Integrating gaseous and liquid radionuclide dispersion across multiple units

Monitoring radioactive releases during the normal operation of power plants is crucial to ensure compliance with safety limits set by regulatory bodies for environmental safety. In the case of the Barakah nuclear power plant in the UAE, comprehensive multiunit dispersion modelling and radiological safety analysis have been conducted. Utilizing the HotSpot Health Physics Code and GENII (Second-generation environmental dosimetry), assessments were made for both 37 gaseous and 51 liquid source terms generated by GALE. Release rates for source terms were determined using GALE based on APR 1400 specifications. HotSpot employed the Gaussian Plume model to simulate the dispersion of gaseous source terms up to 80 km surrounding the plant, calculating Total Effective Dose Equivalent (TEDE) and Committed Effective Dose Equivalent (CEDE) in rural and urban areas. Findings indicated that neither scenario exceeded the 1 mSv threshold for the general public nor the 20 mSv limit for operational workers. Notably, skin, thyroid, and surface bones exhibited the highest CEDE, primarily influenced by iodide radionuclides. GENII's Surface Water module modelled the effects of liquid source terms, accounting for various contamination and exposure pathways such as external exposure and ingestion across different age groups. The calculated doses remained well below FANR's annual limits, with negligible cancer incidences and fatalities predicted for one year of exposure.

Human Biodistribution and Radiation Dosimetry of the Targeting Fibroblast Growth Factor Receptor 1-Positive Tumors Tracer [68Ga]Ga-DOTA-FGFR1-Peptide.

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

Advancing Cancer Theranostics Through Integrin αVβ3-Targeted Peptidomimetic IAC: From Bench to Bedside.

Introduction: The expression of alpha-five beta-three (αVβ3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVβ3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2',2" -{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [68Ga]Ga, [177Lu]Lu, and [225Ac]Ac was optimized. The binding affinity (Kd) of DOTAGA-IAC for the αVβ3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [177Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [68Ga]Ga-DOTAGA-IAC and [18F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [68Ga]Ga-DOTAGA-IAC and [18F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). Kd and Bmax measurements were 15.02 nM and 417 fmol for αVβ3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [177Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30-35 mins postadministration. Out of the cohort, [68Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUVmax) of 3.94 ± 0.58 compared with [18F]FDG (SUVmax 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVβ3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [68Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVβ3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy.

Treatment plan quality on a new slip ring-mounted radiotherapy system for cervical and breast cancer: Dosimetry and plan complexity analysis

PurposeThis study focuses on evaluating the performance of ring-mounted LINAC TAICHI, a novel radiotherapy system, with treatment plans obtained from Raystation TPS (TAICHI-RS), by comparing its plans with those on the C-arm LINAC TrueBeam with Eclipse TPS (TrueBeam-E) in the context of cervical cancer and breast cancer treatments. The study aims to assess the dosimetric results and plan complexity metrics of this new system. Method and materialsThe research randomly selected 13 cervical cancer and 11 breast cancer patients treated with VMAT on the TAICHI LINAC. The plans were reproduced in Eclipse TPS for the TrueBeam LINAC using the same CT and structure sets. Dosimetric metrics, including dose distribution in the target volume and the dose received by OARs, were analyzed. Complexity metrics were also assessed to evaluate plan complexity. In addition, patient-specific quality assurance (PSQA) was measured for both TAICHI-RS and TrueBeam-E systems. ResultsResults have shown that in cervical cancer plans, both systems performed similarly in terms of OARs. In breast cancer plans, TAICHI-RS system demonstrated significant advantages, achieving better dose homogeneity, lower irradiated doses in OARs, and more uniform dose distributions in the target volume compared to TrueBeam-E system (P values < 0.05). Complexity metrics indicated that for cervival cancer, TAICHI-RS plans were generally more complex than TrueBeam-E plans, while they were similar for breast cancer. The average PSQA passing rates of TAICHI-RS versus TrueBeam-E systems were 98.5% versus 98.7% (2%/2 mm criteria) and 99.9% versus 99.9% (3%/3 mm criteria) for cervival cancer plans, and 95.7% versus 97.4% (2%/2 mm criteria) and 99.3% versus 99.5% (3%/3 mm criteria) for breast cancer plans respectively. ConclusionIn conclusion, the new TAICHI-RS system was demonstrated to be clinically useful and accurate in delivering treatment plans for cervical and breast cancer. The study suggests that TAICHI-RS system could offer advantages in breast cancer treatments particularly. Further multi-center research is recommended for comprehensive validation.

Establishing Updated Safety Standards for Independent 99mTc-MAA SPECT/CT Treatment Planning in Radioembolization

Significant improvements within radioembolization imaging and dosimetry permit the development of an accurate and personalized pretreatment plan using technetium 99m-labeled macroaggregated albumin (99mTc-MAA) and single-photon emission computed tomography (SPECT) combined with anatomical CT (SPECT/CT). Despite these potential advantages, the clinical transition to pretreatment protocols with SPECT/CT is hindered by their unknown safety constraints. This study aimed to address this issue by establishing novel dose limits for 99mTc-MAA SPECT/CT to enable quantitative pretreatment planning. Stratification criteria to determine images most viable for dosimetry analysis were created from a cohort of 85 patients. SPECT/CT, cone beam CT, and activity calculations derived from the local deposition method were used to create an accurate pretreatment protocol. Planar and SPECT/CT images were compared using linear regression and modified Bland-Altman analyses to convert accepted planar dose limits to SPECT/CT. To validate these new dose limits, activity calculations based on SPECT/CT were compared with those calculated with the body surface area and planar methods for three treatment plans. A total of 38 of 85 patients were deemed viable for dosimetry analysis. SPECT yielded greater lung shunt fractions (LSFs) than planar imaging when LSFs were <4.89%, whereas SPECT yielded lower LSFs than planar imaging when LSFs were >4.89%. Planar to SPECT/CT dose conversions were 0.76×, 0.70×, and 0.55× for the whole liver, normal liver, and lungs, respectively. Patients with SPECT LSFs ≤4.89% were safely treated with the direct application of planar lung dose limits. Activity calculations with the newly established SPECT/CT dose limits were greater than those of the body surface area method by a median range of 33.1% to 61.9% and were lower than planar-based activity calculations by a median range of 12.5% to 13.7% for the whole liver and by 29.4% to 32.2% for the normal liver. This study demonstrated a safe method for translating dose limits from 99mTc-MAA planar imaging to SPECT/CT. A robust pretreatment protocol was further developed guided by the current knowledge in the field. Established SPECT/CT dose limits safely treated 97.5% of patients and permitted the application of independent pretreatment planning with 99mTc-MAA SPECT/CT.

Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab: a phase 1 clinical study in Japanese patients with renal cell carcinoma (Zirdac-JP).

PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. Eligible adult patients received 37MBq (± 10%; 10mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72h and Day 5±2d after administration. [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean±standard deviation) (1.365±0.245mGy/MBq), kidney (1.126±0.190mGy/MBq), heart wall (1.096±0.232mGy/MBq), and spleen (1.072±0.466mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

Feasibility of a Tungsten-181 HDR brachytherapy source: Analysis of isotope production and source dosimetry

BackgroundInterest in Intensity Modulated Brachytherapy (IMBT) for High Dose Rate Brachytherapy (HDR) treatments has steadily increased in recent years. However, intensity modulation is not best optimized for currently used HDR sources since they emit high energy photons. To that end, the focus on IMBT has moved to middle energy sources, such as Ytterbium-169; yet even Yb-169 emits some high energy photons at a low yield. We present an alternative isotope, Tungsten-181 (T1/2 = 121 days) that is interesting due to its complete lack of high energy photon emissions. (Eavg = 58.9 keV, Emed = 57.5 keV) making it potentially favorable as high dose rate brachytherapy source from both a medical physics and health physics perspective. PurposeThe purpose of this study was to determine the feasibility of using W-181 as an HDR brachytherapy source; in this study we focused on W-181's production, dosimetric properties, and intensity modulation capabilities. MethodsWe determined the isotope production kinetics, its Dose Rate Constant, Radial Dose Function, photon self-absorption, and the shielding intensity modulation capabilities for a W-181 pellet source geometry using the MCNP6.2 Computer Simulations Code. All simulations were performed using a personal computer running an AMD Ryzen 5 3600 6-Core Processor 3.59 GHz. The number of histories run for each study were selected to produce relative simulation convergence errors in the MCNP tally output of less than 2%.Dosimetric calculations were made using the MCNP6.2 computer simulations code and activation analyses were determined mathematically using a Catenary kinetics analysis (also known as a Bateman Analysis) of W-181 and Tantlum-182 production from the neutron activation of a pure Tungsten-180 stable target. Since W-181 emits middle energy photons and has a high density, we also assessed the effects of photon self-absorption within a tungsten pellet. ResultsFrom our analysis, we determined that a 3.5 mm long and 0.6 mm in diameter is feasible for clinical applications. Our activation analyses found that these pellets can achieve W-181 activities up to 7.9Ci and 13Ci using neutron fluence rates of 4E14 cm−2 s−1 and 1E15 cm−2 s−1 respectively, which then would provide a dose rate of 1.84 ± 0.01 cG y/Ci/min at a depth of 1 cm from the source. Using our resulting Monte Carlo simulated Dose Rate Constant of 1.24 ± 0.02 cGy h−1∙U−1, a W-181 source in this geometry would require a source activity upwards of 10Ci for use in HDR treatments. In the intensity modulation analysis, only 0.1 mm of gold shielding was found to reduce a pellet's absorbed dose by over 50% while 0.3 mm of gold shielding, which is thin enough to theoretically fit between an HDR pellet and the inner catheter wall, was found to reduce the pellet's absorbed dose by over 85%. ConclusionsWhile W-181 has a lower specific activity than Ir-192 and Yb-169, it shows great promise as an isotope for use in Intensity Modulated Brachytherapy due to its easily shielded photons. We therefore expect that W-181 may lend itself best for use as a multi-pellet configuration in IMBT.

Second harmonic generation microscopy of electromechanical reshaping on corneal collagen

Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

Assessing Response to PSMA Radiopharmaceutical Therapies with Single SPECT Imaging at 24 Hours After Injection.

Understanding the relationship between lesion-absorbed dose and tumor response in 177Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing 177Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECTmean, SPECTmaximum, and SPECTVIP-PSMA, respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECTmean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECTmaximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECTVIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECTVIP-PSMA response (R 2 = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response (R 2 = 0.05, P = 0.001, and R 2 = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations.

Utilizing collimated aperture with proton pencil beam scanning (PBS) for stereotactic radiotherapy.

Proton stereotactic radiosurgery (PSRS) has emerged as an innovative proton therapy modality aimed at achieving precise dose delivery with minimal impact on healthy tissues. This study explores the dosimetric outcomes of PSRS in comparison to traditional intensity-modulated proton therapy (IMPT) by focusing on cases with small target volumes. A custom-made aperture system designed for proton therapy, specifically tailored to small target volumes, was developed and implemented for this investigation. A prerequisite mechanical validation through an isocentricity test precedes dosimetric assessments, ensuring the seamless integration of mechanical and dosimetry analyses. Five patients were enrolled in the study, including two with choroid melanoma and three with arteriovenous malformations (AVM). Two treatment plans were meticulously executed for each patient, one utilizing a collimated aperture and the other without. Both plans were subjected to robust optimization, maintaining identical beam arrangements and consistent optimization parameters to account for setup errors of 2mm and range uncertainties of 3.5%. Plan evaluation metrics encompassing the Heterogeneity Index (HI), Paddick Conformity Index (CIPaddick), Gradient Index (GI), and the R50% index to evaluate alterations in low-dose volume distribution. The comparative analysis between PSRS and traditional PBS treatment revealed no significant differences in plan outcomes, with both modalities demonstrating comparable target coverage. However, collimated apertures resulted in discernible improvements in dose conformity, dose fall-off, and reduced low-dose volume. This study underscores the advantageous impact of the aperture system on proton therapy, particularly in cases involving small target volumes.

Abstract 1119: Novel fibroblast activation protein targeting radioligand for imaging and radiotherapy of solid tumors

Abstract Fibroblast activation protein has emerged as an attractive biomarker for the imaging and therapyof ~90% of human epithelial cancers due to its expression on cancer associated fibroblasts (CAFs), but not on fibroblasts in healthy tissues. Not surprisingly, several small molecules and peptide-based radioligands that target FAP have been introduced into human clinical trials, but preclinical and clinical data suggest that these radioligand therapies suffer from inadequate tumor uptake, short tumor residence times, or unwanted uptake in the healthy tissues. Hence, there remains an unmet need for development of new FAP-targeted radioligands with improved therapeutic properties. For this purpose, we have designed and synthesized a higher affinity and specificity FAP-targetingligand (FAP8) and linked this ligand via a PEG spacer to both a well-known metal chelator (DOTA)and a 4(-iodo)-phenyl butyric acid pharmacokinetic extender to yield the trifunctional conjugate, FAP8-IP-DOTA. Binding affinity and FAP specificity studies reveal that FAP8-IP-DOTA exhibits high affinity and selectivity for FAP (IC50 = 1.6 nM) relative to its ubiquitous homologs’ prolyloligopeptidase (IC50 = 16.5 nM) and dipeptidyl peptidase-IV (IC50 = 865.0 nM). Moreover, 177Luand 111In radiolabeled forms of the conjugate were found to bind a FAP-transduced cell line (HEK-FAP) with a Kd = 3.0 ± 2 nM, and this binding was completely suppressed upon co-incubation with unlabeled conjugate, i.e., further confirming FAP’s specificity. SPECT/CT imaging studies following intravenous injection of 111In labelled FAP8-IP-DOTA into mice expressing HT29, MDA-MB-231, KB or 4T1 tumors then demonstrated high tumor uptake and remarkably prolonged tumor retention of &amp;gt;8 days. Biodistribution studies of the 177Lu labelledFAP8-IP-DOTA conjugate in mice implanted with either FAP-negative 4T1 tumor cells or FAP-transduced HEK tumor cells at different time points further revealed declining tumor radioactivity from 12.0 to 2.0 % ID/g and 21.0 to 12.0 %ID/g between 1h and 168h post injection, respectively. Importantly, uptake of the same conjugate in the healthy tissues was minimal over this time course, with most radioactivity clearing rapidly. Comparative dosimetry analyses showed tumor: healthy tissues ratios of &amp;gt;5-fold for all major organs. Finally, analysis of tumor inhibiting activity demonstrated that 177Lu-FAP8-IP-DOTA suppressed tumor growth between 60% and 100% in all xenograft models tested (HT29, MDA-MB-231, KB and 4T1), with remarkably improved overall survival rates compared to untreated groups. Based on these promising results, we suggest that FAP8-IP-DOTA warrants further evaluation for possible translation into human clinical trials. Citation Format: Ramesh Mukkamala, Lindemann D. Spencer, Carlson J. Daniel, Pooja Tudi, Miller Nicholas Kaine, Autumn Horner, Srinivasarao Madduri, Philip S. Low. Novel fibroblast activation protein targeting radioligand for imaging and radiotherapy of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1119.

155Tb production by cyclotrons: what level of 155Gd enrichment allows clinical applications?

Background155Tb represents a potentially useful radionuclide for diagnostic medical applications, but its production remains a challenging problem, in spite of the fact that many production routes have been already investigated and tested. A recent experimental campaign, conducted with low-energy proton beams impinging on a 155Gd target with 91.9% enrichment, demonstrated a significant co-production of 156gTb, a contaminant of great concern since its half-life is comparable to that of 155Tb and its high-energy γ emissions severely impact on the dose released and on the quality of the SPECT images. In the present investigation, the isotopic purity of the enriched 155Gd target necessary to minimize the co-production of contaminant radioisotopes, in particular 156gTb, was explored using various computational simulations.ResultsStarting from the recent experimental data obtained with a 91.9% 155Gd-enriched target, the co-production of other Tb radioisotopes besides 155Tb has been theoretically evaluated using the Talys code. It was found that 156Gd, with an isotopic content of 5.87%, was the principal contributor to the co-production of 156gTb. The analysis also demonstrated that the maximum amount of 156Gd admissible for 155Tb production with a radionuclidic purity higher than 99% was 1%. A less stringent condition was obtained through computational dosimetry analysis, suggesting that a 2% content of 156Gd in the target can be tolerated to limit the dose increase to the patient below the 10% limit. Moreover, it has been demonstrated that the imaging properties of the produced 155Tb are not severely affected by this level of impurity in the target.Conclusions155Tb can be produced with a quality suitable for medical applications using low-energy proton beams and 155Gd-enriched targets, if the 156Gd impurity content does not exceed 2%. Under these conditions, the dose increase due to the presence of contaminant radioisotopes remains below the 10% limit and good quality images, comparable to those of 111In, are guaranteed.

Modeling of a tissue expander with a radiofrequency identification port in postmastectomy radiation therapy planning.

The purpose of this study was to evaluate the dose attenuation of Motiva Flora® (Flora, Establishment Labs, Alajuela, Costa Rica) tissue expander with a radiofrequency identification port locator and to develop a model for accurate postmastectomy radiation therapy planning. Dose attenuation was measured using an EBT3 film (Ashland, Bridgewater, NJ), and the optimal material and density assignment for the radiofrequency identification coil for dose calculation were investigated using the AcurosXB algorithm on the Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system. Additionally, we performed in vivo dosimetry analysis using irradiation tangential to the Flora tissue expander to validate the modeling accuracy. Dose attenuations downstream of the Flora radiofrequency identification coil was 1.29% for a 6 MV X-ray and 0.99% for a 10 MV X-ray when the coil was placed perpendicular to the beam. The most suitable assignments for the material and density of the radiofrequency identification coil were aluminum and 2.27g/cm3, respectively, even though the coil was actually made of copper. Gamma analysis of in vivo dosimetry with criteria of 3% and 2mm did not fail in the coil region. Therefore, we conclude that the model is reasonable for clinical use.

Analysis of external personal dosimetry for external ex-posure to medical radiation workers in radiotherapy and nuclear medicine departments between 2019 and 2022

The National Cancer Institute from Chile possesses a wide variety of high-complexity equipment for cancer treatment and diagnosis that employs ionizing radiation with high and medium energy. Presently, the radiotherapy department is equipped with 5 clinical linear accelerators and one brachytherapy equipment, while the nuclear medicine department is equipped with a PET-CT, a single gamma camera, and a hospitalization room for betatherapy. A descriptive statistical analysis was conducted on the Personal Doses Equivalent Reports from medical radiation workers between 2019-2022. The analysis involved extracting Hp(10) and Hp(0.07) measurements from digital reports using the Python Pandas library, and a database was constructed. The annual set of data was selected for each department to describe their behavior concerning Hp(10) total since PD8 dosimeters had the highest circulation. Additionally, using the boxplot format for the Hp(10) and Hp(0.07) distributions, means, medians, minimums and maximums, interquartile ranges and outliers were analyzed. While Hp(10) measurements exhibited an increase, Hp(0.07) measurements remained constant or experienced a decrease. All reported measurements were less than international tolerances. Finally, this initial descriptive statistical analysis enables the radiation safety officers to evaluate the applicability of inferential statistical analysis with stronger evidence and in an objective manner.

A reinforcement learning agent for head and neck intensity-modulated radiation therapy

Head and neck (HN) cancers pose a difficult problem in the planning of intensity-modulated radiation therapy (IMRT) treatment. The primary tumor can be large and asymmetrical, and multiple organs at risk (OARs) with varying dose-sparing goals lie close to the target volume. Currently, there is no systematic way of automating the generation of IMRT plans, and the manual options face planning quality and long planning time challenges. In this article, we present a reinforcement learning (RL) model for the purposes of providing automated treatment planning to reduce clinical workflow time as well as providing a better starting point for human planners to modify and build upon. Several models with progressing complexity are presented, including the relevant plan dosimetry analysis and model interpretations of the resulting strategies learned by the auto-planning agent. Models were trained on a set of 40 patients and validated on a set of 20 patients. The presented models are shown to be consistent with the requirements of an RL model to be underpinned by a Markov decision process (MDP). In-depth interpretability of the models is presented by examination of the decision space using action hyperplanes. The auto-planning agent was able to generate plans with superior reduction in the mean dose of the left and right parotid glands by approximately 7 Gy ± 2.5 Gy (p &amp;lt; 0.01) over a starting, static template plan with only pre-defined general prescription information. RL plans were comparable to a human expert’s clinical plans for the primary (44 Gy), boost (26 Gy) , and the summed plans (70 Gy) with p-values of 0.43, 0.72, and 0.67, respectively, for the dosimetric endpoints and uniform target coverage normalization. The RL planning agent was able to produce the plans used in validation in an average of 13.58 min, with a minimum and a maximum planning time of 2.27 and 44.82 min, respectively.

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac: Estimated delivered dose and early toxicity results.

Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac. Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis. Chinese Clinical Trial Registry ChiCTR2000033382.

Evaluation of radiological capacity and usage in paediatric TB diagnosis: A mixed-method protocol of a comparative study in Mozambique, South Africa and Spain.

Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited. A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum. As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management.