scholarly journals Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3884
Author(s):  
Jens Kurth ◽  
Martin Heuschkel ◽  
Alexander Tonn ◽  
Anna Schildt ◽  
Oliver W. Hakenberg ◽  
...  
Keyword(s):  
Organs At Risk ◽  
Quantitative Imaging ◽  
Absorbed Dose ◽  
Dose Calculation ◽  
Reference Method ◽  
Whole Body ◽  
Parotid Glands ◽  
Quantitative Spect ◽  
Calculation Results ◽  
Kinetics Of

(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [177Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this calculation, results and kinetics of the first therapy cycle were used. (Methods) 46 patients treated with 2 to 6 cycles of [177Lu]Lu-PSMA-617 were included. As reference (current clinical standard) full dosimetry of the OAR based on quantitative imaging (whole body scintigraphy and quantitative SPECT/CT at 2, 24, 48 and 72 h p.i.) for every cycle was used. Alternatively, two dosimetry schemes, simplified in terms of image acquisition and dose calculation, were established, both assuming nearly unchanged kinetics of the radiopharmaceutical for subsequent cycles. (Results) In general, for both OAR the simplified methods provided results that were consistent with the dosimetric reference method, both per cycle and in terms of cumulative AD. Best results were obtained when imaging was performed at 48 h p.i. in each of the subsequent cycles. However, both simplified methods tended to underestimate the cumulative AD. (Conclusion) Simplified dosimetry schemes are feasible to tailor multi-cycle [177Lu]Lu-PSMA-targeted therapies.

scholarly journals Feasibility study of volumetric modulated arc therapy with Halcyon™ linac for total body irradiation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takuya Uehara ◽  
Hajime Monzen ◽  
Mikoto Tamura ◽  
Masahiro Inada ◽  
Masakazu Otsuka ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Organs At Risk ◽  
Volumetric Modulated Arc Therapy ◽  
Dose Calculation ◽  
Target Volume ◽  
The Body ◽  
Whole Body ◽  
Data Set ◽  
Arc Therapy ◽  
Total Body

Abstract Background The use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI. Methods VMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes. Results The PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1–2 h. Dose calculation and optimization was performed for 3–4 h. Quality assurance (QA) took 2–3 h. The treatment duration was 23 min. Conclusions A planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.

scholarly journals Dosimetry of 177Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 621 ◽  
Author(s):  
Anna Sarnelli ◽  
Maria Belli ◽  
Valentina Di Iorio ◽  
Emilio Mezzenga ◽  
Monica Celli ◽  
...  
Keyword(s):  
Dose Calculation ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Parotid Glands ◽  
Castration Resistant ◽  
Red Marrow ◽  
Dosimetric Data ◽  
Significant Difference ◽  
Post Infusion ◽  
Prospective Phase

Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

scholarly journals [68Ga]Ga-PSMA-11 PET imaging as a predictor for absorbed doses in organs at risk and small lesions in [177Lu]Lu-PSMA-617 treatment

2021 ◽  
Author(s):  
Steffie M. B. Peters ◽  
Regina Hofferber ◽  
Bastiaan M. Privé ◽  
Maarten de Bakker ◽  
Martin Gotthardt ◽  
...  
Keyword(s):  
At Risk ◽  
Patient Selection ◽  
Organs At Risk ◽  
Absorbed Dose ◽  
Target Volume ◽  
Tracer Uptake ◽  
Parotid Glands ◽  
Dose Ratio ◽  
Psma Pet ◽  
Pet Ct

Abstract Introduction Patient eligibility for [177Lu]Lu-PSMA therapy remains a challenge, with only 40–60% response rate when patient selection is done based on the lesion uptake (SUV) on [68Ga]Ga-PSMA-PET/CT. Prediction of absorbed dose based on this pre-treatment scan could improve patient selection and help to individualize treatment by maximizing the absorbed dose to target lesions while adhering to the threshold doses for the organs at risk (kidneys, salivary glands, and liver). Methods Ten patients with low-volume hormone-sensitive prostate cancer received a pre-therapeutic [68Ga]Ga-PSMA-11 PET/CT, followed by 3 GBq [177Lu]Lu-PSMA-617 therapy. Intra-therapeutically, SPECT/CT was acquired at 1, 24, 48, 72, and 168 h. Absorbed dose in organs and lesions (n = 22) was determined according to the MIRD scheme. Absorbed dose prediction based on [68Ga]Ga-PSMA-PET/CT was performed using tracer uptake at 1 h post-injection and the mean tissue effective half-life on SPECT. Predicted PET/actual SPECT absorbed dose ratios were determined for each target volume. Results PET/SPECT absorbed dose ratio was 1.01 ± 0.21, 1.10 ± 0.15, 1.20 ± 0.34, and 1.11 ± 0.29 for kidneys (using a 2.2 scaling factor), liver, submandibular, and parotid glands, respectively. While a large inter-patient variation in lesion kinetics was observed, PET/SPECT absorbed dose ratio was 1.3 ± 0.7 (range: 0.4–2.7, correlation coefficient r = 0.69, p < 0.01). Conclusion A single time point [68Ga]Ga-PSMA-PET scan can be used to predict the absorbed dose of [177Lu]Lu-PSMA therapy to organs, and (to a limited extent) to lesions. This strategy facilitates in treatment management and could increase the personalization of [177Lu]Lu-PSMA therapy.

Effect of ionizing radiation on the kinetics of hydrogenation on the Ni-MgO mixed catalyst

1982 ◽  
Vol 47 (7) ◽  
pp. 1780-1786 ◽  
Author(s):  
Rostislav Kudláček ◽  
Jan Lokoč
Keyword(s):  
Experimental Data ◽  
Activation Energy ◽  
Liquid Phase ◽  
Ionizing Radiation ◽  
Oxide Catalyst ◽  
Absorbed Dose ◽  
Hydrogenation Rate ◽  
Solution Composition ◽  
Mixed Catalyst ◽  
Kinetics Of

The effect of gamma pre-irradiation of the mixed nickel-magnesium oxide catalyst on the kinetics of hydrogenation of maleic acid in the liquid phase has been studied. The changes of the hydrogenation rate are compared with the changes of the adsorbed amount of the acid and with the changes of the solution composition, activation energy, and absorbed dose of the ionizing radiation. From this comparison and from the interpretation of the experimental data it can be deduced that two types of centers can be distinguished on the surface of the catalyst under study, namely the sorption centres for the acid and hydrogen and the reaction centres.

scholarly journals Optimization of SPECT/CT imaging protocols for quantitative and qualitative 99mTc SPECT

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Dennis Kupitz ◽  
Heiko Wissel ◽  
Jan Wuestemann ◽  
Stephanie Bluemel ◽  
Maciej Pech ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Quantitative Imaging ◽  
Scatter Correction ◽  
Reconstruction Algorithm ◽  
Weighting Factor ◽  
Quantitative Spect ◽  
Pet Ct ◽  
Spect Acquisition ◽  
The Mean ◽  
A Minor

Abstract Background The introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol. Results The reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by − 13.9 kBq/ml (− 16.3%) and − 7.1 kBq/ml (− 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = − 14.6 kBq/ml (− 17.1%), 240 iterations (24i/10s) = − 8.0 kBq/ml (− 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001). Conclusion Quantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

scholarly journals Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Julia Brosch-Lenz ◽  
Carlos Uribe ◽  
Astrid Gosewisch ◽  
Lena Kaiser ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Organs At Risk ◽  
Bone Lesion ◽  
Absorbed Dose ◽  
Hounsfield Unit ◽  
Outcome Data ◽  
Computational Effort ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Percentage Difference ◽  
Density Weighting

Abstract Background Patients with metastatic, castration-resistant prostate cancer (mCRPC) present with an increased tumor burden in the skeleton. For these patients, Lutetium-177 (Lu-177) radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has gained increasing interest with promising outcome data. Patient-individualized dosimetry enables improvement of therapy success with the aim of minimizing absorbed dose to organs at risk while maximizing absorbed dose to tumors. Different dosimetric approaches with varying complexity and accuracy exist for this purpose. The Medical Internal Radiation Dose (MIRD) formalism applied to tumors assumes a homogeneous activity distribution in a sphere with unit density for derivation of tumor S values (TSV). Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) absorbed dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density weighting has the potential to overcome the assumption of homogeneous density in the MIRD formalism with TSV and VSV methods, which could be a major limitation for the application in bone metastases with heterogeneous density. The aim of this investigation is a comparison of these methods for bone lesion dosimetry in mCRPC patients receiving Lu-177-PSMA therapy. Results In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage difference (PD) of average absorbed dose per lesion compared to MC, averaged over all lesions, was + 14 ± 10% (min: − 21%; max: + 56%) for TSVs. With lesion-individual density weighting using Hounsfield Unit (HU)-to-density conversion on the patient’s CT image, PD was reduced to − 8 ± 1% (min: − 10%; max: − 3%). PD on a voxel level for three-dimensional (3D) voxel-wise dosimetry methods, averaged per lesion, revealed large PDs of + 18 ± 11% (min: − 27%; max: + 58%) for a soft tissue VSV approach compared to MC; after voxel-wise density correction, this was reduced to − 5 ± 1% (min: − 12%; max: − 2%). Conclusion Patient-individual MC absorbed dose simulation is capable to account for heterogeneous densities in bone lesions. Since the computational effort prevents its routine clinical application, TSV or VSV dosimetry approaches are used. This study showed the necessity of lesion-individual density weighting for TSV or VSV in Lu-177-PSMA therapy bone lesion dosimetry.

scholarly journals Building Large-Scale Quantitative Imaging Databases with Multi-Scale Deep Reinforcement Learning: Initial Experience with Whole-Body Organ Volumetric Analyses

2021 ◽  
Vol 34 (1) ◽  
pp. 124-133
Author(s):  
David J. Winkel ◽  
Hanns-Christian Breit ◽  
Thomas J. Weikert ◽  
Bram Stieltjes
Keyword(s):  
Reinforcement Learning ◽  
Repeated Measures ◽  
Quantitative Imaging ◽  
Left Kidney ◽  
Left Lung ◽  
Whole Body ◽  
Computational Time ◽  
Slice Thickness ◽  
Multi Scale ◽  
Body Organ

AbstractTo explore the feasibility of a fully automated workflow for whole-body volumetric analyses based on deep reinforcement learning (DRL) and to investigate the influence of contrast-phase (CP) and slice thickness (ST) on the calculated organ volume. This retrospective study included 431 multiphasic CT datasets—including three CP and two ST reconstructions for abdominal organs—totaling 10,508 organ volumes (10,344 abdominal organ volumes: liver, spleen, and kidneys, 164 lung volumes). Whole-body organ volumes were determined using multi-scale DRL for 3D anatomical landmark detection and 3D organ segmentation. Total processing time for all volumes and mean calculation time per case were recorded. Repeated measures analyses of variance (ANOVA) were conducted to test for robustness considering CP and ST. The algorithm calculated organ volumes for the liver, spleen, and right and left kidney (mean volumes in milliliter (interquartile range), portal venous CP, 5 mm ST: 1868.6 (1426.9, 2157.8), 350.19 (45.46, 395.26), 186.30 (147.05, 214.99) and 181.91 (143.22, 210.35), respectively), and for the right and left lung (2363.1 (1746.3, 2851.3) and 1950.9 (1335.2, 2414.2)). We found no statistically significant effects of the variable contrast phase or the variable slice thickness on the organ volumes. Mean computational time per case was 10 seconds. The evaluated approach, using state-of-the art DRL, enables a fast processing of substantial amounts irrespective of CP and ST, allowing building up organ-specific volumetric databases. The thus derived volumes may serve as reference for quantitative imaging follow-up.

scholarly journals Use of a Head-Tilting Baseplate During Tomotherapy to Shorten the Irradiation Time and Protect the Hippocampus and Lens in Hippocampal Sparing-Whole Brain Radiotherapy

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Kosei Miura ◽  
Hiromasa Kurosaki ◽  
Nobuko Utsumi ◽  
Hideyuki Sakurai
Keyword(s):  
At Risk ◽  
Planning Target Volume ◽  
Irradiation Time ◽  
Organs At Risk ◽  
Absorbed Dose ◽  
Whole Brain Radiotherapy ◽  
Target Volume ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Hippocampal Sparing

Purpose: The aim of this study is to comparatively examine the possibility of reducing the exposure dose to organs at risk, such as the hippocampus and lens, and improving the dose distribution of the planned target volume with and without the use of a head-tilting base plate in hippocampal-sparing whole-brain radiotherapy using tomotherapy. Methods: Five paired images of planned head computed tomography without and with tilt were analyzed. The hippocampus and planning target volume were contoured according to the RTOG 0933 contouring atlas protocol. The hippocampal zone to be avoided was delineated using a 5-mm margin. The prescribed radiation dose was 30 Gy in 10 fractions. The absorbed dose to planning target volume dose, absorbed dose to the organ at risk, and irradiation time were evaluated. The paired t-test was used to analyze the differences between hippocampal-sparing whole-brain radiotherapy with head tilts and without head tilts. Results: Hippocampal-sparing whole-brain radiotherapy with tilt was not superior in planning target volume doses using the homogeneity index than that without tilt; however, it showed better values, and for Dmean and D2%, the values were closer to 30 Gy. Regarding the hippocampus, dose reduction with tilt was significantly greater at Dmax, Dmean, and Dmin, whereas regarding the lens, it was significantly greater at Dmax and Dmin. The irradiation time was also predominantly shorter. Conclusion: In our study, a tilted hippocampal-sparing whole-brain radiotherapy reduced the irradiation time by >10%. Therefore, our study indicated that hippocampal-sparing whole-brain radiotherapy with tomotherapy should be performed with a tilt. The head-tilting technique might be useful during hippocampal-sparing whole-brain radiotherapy. This method could decrease the radiation exposure time, while sparing healthy organs, including the hippocampus and lens.

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