| 1. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Dosimetric analysis of the short-ranged particle emitter161 tb for radionuclide therapy of metastatic prostate cancer
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq ) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 2. |
- Hagmarker, Linn, et al.
(författare)
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Characterisation of a planar dosimetry method estimating the absorbed dose to the bone marrow during 177Lu-DOTATATE treatment
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: An image based method for bone marrow dosimetry, earlier presented by our research group, has shown a significant correlation between the absorbed dose to the bone marrow and haematological toxicity in 177Lu-DOTATATE treatment. The aim of this study was to further evaluate and optimise the method. Materials and Methods: 46 patients with advanced neuroendocrine tumours were treated with 177Lu -DOTATATE on 2-6 occasions. The patients were evaluated using the 4 planar gamma camera images collected at 2, 24, 48 and 168 hours after injection. The whole body was divided into a high- and a low uptake compartment, using a threshold based segmentation tool in the image platform PhONSAi, developed in-house. The segmentation tool starts by including the highest uptake focus and then gradually includes foci with lower and lower uptakes until a threshold is reached where the number of foci escalates. The threshold determines the proportion of the foci that is included in the two compartments. Visual inspection was used to determine the threshold valuewhere all high uptake tissues (i.e. kidney, spleen, liver and tumours) were included in the high uptake compartment. For thresholds around this value the activity in the two compartments was determined by the conjugate view method and the bonemarrow dose was calculated as a sum of the self and cross dose in the low uptake compartment and the cross dose from the high uptake compartment. Results: The visual analysis implies a threshold value of 10%of the maximum number of foci. A correlation was found between the absorbed bone marrow dose and haematological toxicity with p-values ranging from 0.001 to 0.02 for thresholds between 2 % and 25 %, the strongest correlation was found at 15 %. The mean absorbed bone marrow dose were 0.20-0.22 Gy per 7.4 GBq for threshold values between 10-25 %, and increased to 0.28 Gy for the lower values. No significant difference was observed in coefficient of variation (8.2-8.7 %) for the individual mean absorbed doses when varying the threshold value. Conclusion: The individual variation in absorbed dose is maintained at a low level when varying the threshold value for the determination of the compartment sizes. This implies that the method is stable for estimation of bone marrow doses and its correlation to haematological toxicity.
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| 3. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90.
- 2022
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Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Based on theoretical and preclinical results, terbium-161 may be a valid alternative to lutetium-177 and yttrium-90 in radionuclide therapies. The large low-energy electron emission from terbium-161 is a favorable feature in the treatment of disseminated disease, but its impact on the radiosensitive bone marrow needs to be evaluated. Using voxel-based skeletal dosimetry models in which active bone marrow is defined as regions containing stem cells and progenitor cells of the hematopoietic lineage, we generated S-values (absorbed dose per decay) for terbium-161 and evaluated its distribution-dependence in bone marrow cavities.S-values in the active bone marrow were calculated for terbium-161, lutetium-177, and yttrium-90 irradiation using two (male/female) image-based bone marrow dosimetry models. The radionuclides were distributed to one of the three structures that define the spongiosa bone region in the skeletal models: (i) active bone marrow, (ii) inactive bone marrow, or (iii) surface or whole volume of the trabecular bone. Decay data from ICRP 107 were combined with specific absorbed fractions to calculate S-values for 13 skeletal sites. To increase the utility, the skeletal site-specific S-values were averaged to produce whole-body average S-values and spongiosa average S-values.For yttrium-90, the high-energy β particles irradiate the active marrow regardless of the source compartment, consistently generating the highest S-values (65-90% higher). Between terbium-161 and lutetium-177, the largest differences in S-values were with an active marrow source (50%), such as self-irradiation, due to the contribution of the short-ranged conversion and Auger electrons from terbium-161. Their influence decreased as the source moved to inactive marrow or the surface or volume of the trabecular bone, reducing the S-values and the differences between terbium-161 and lutetium-177 (15-35%).The S-values of terbium-161 for active bone marrow and, consequently, the bone marrow toxicity profile were more dependent on the radionuclide distribution within the bone marrow cavity than the S-values of lutetium-177 and yttrium-90. This effect was attributed to the considerable low-energy electron emission of terbium-161. Therefore, it will be critical to investigate the bone marrow distribution of a particular radiopharmaceutical for accurate estimation of the active bone marrow dose.
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| 4. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities
- 2018
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
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| 5. |
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| 6. |
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| 7. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Simulation of 90Y microspheres in selective internal radiation therapy (SIRT) reveals different heterogeneity profiles for glass and resin microspheres.
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. 43 (Suppl 1): 1. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: Selective internal radiation therapy (SIRT) can supply normal tissue in the liver with radiation doses exceeding tolerance without causing toxicity, an effect possibly explained by microsphere clustering causing heterogeneity in the distribution. Using a simulation of microspheres transported through a simplified arterial structure, the aim of this study has been to evaluate how the number of injected microspheres affect the dose distribution. Materials and methods: The simulation was based on observations in biopsies and autoradiographies from resected liver tissue receiving 90YSIRT. Individual microspheres, with diameter and density from literature, were followed through a simplistic bifurcations model in which three parameters were introduced and optimised to obtain results consistent with observations: an artery coefficient of variation, a reduction parameter for the arterial diameter and a distribution volume parameter for the arterial tree. In the model the arterial diameter decreases for higher artery generations and the probability of microsphere clustering increases successively in the artery tree. After simulation a 90Y dose kernel was applied to the 940 cm3 sized 3D-matrix of microspheres and the dose distribution throughout the matrix was evaluated using varying resolutions and computing the coefficient of variation (CV). A smaller number of simulated microspheres (10^5) corresponds to the higher activity/sphere found in glass spheres while a larger number (10^7) resembles resin spheres. Results: As the number of microspheres increase from thousands to 106 the CV of the absorbed dose decrease from over 80 % to 32 % in a volume corresponding to a lobuli (2 mm^3) and at 106 microspheres a plateau was reached. The simulation was consistent with biopsy and autoradiography observations regarding the formation of clusters. A large majority of the clusters contain few microspheres and a minority of the clusters are significantly more numerous in microspheres. Conclusion: For the high microsphere concentrations used with resin microspheres the CVof the absorbed doses was constant (32 %) while for the lower microsphere concentrations used for glass spheres the CV varied between 90 % and 40 %. These results implies that small scale dosimetry for 90Y-SIRT differs between resin and glass spheres.
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| 8. |
- Hemmingsson, Jens, 1986
(författare)
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Small-scale dosimetry methods for normal tissues after radioembolization and peptide receptor radiotherapies; a focus on the liver parenchyma and the bone marrow
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radionuclide therapies are increasingly used in cancer treatments as they have been proven to be both effective and safe. As biodistributions and uptake vary widely between patients, a standardized approach is bound to leave a fraction of patients overtreated or undertreated. Dosimetry-based evidence suggests treatment regimens could be improved on a patient-specific basis as the absorbed dose limits for critical organs are not always reached. This thesis has investigated two radionuclide therapies with distinctly different targeting mechanisms and has aimed at investigating the absorbed dose distributions in tumor tissue and the parenchyma of the liver after radioembolization and the radiosensitive red marrow after peptide receptor radionuclide therapy (PRRT). In the first study, a patient with hepatocellular carcinoma underwent radioembolization prior to tumor resection with the aim of reducing the probability of tumor recurrence within the resection boundaries. Using SPECT images, autoradiography, and biopsies, the absorbed dose distribution was evaluated. The analysis revealed a low absorbed dose and a small coefficient of variation in the liver parenchyma. However, the distribution in the tumor showed high levels of heterogeneity, with the greatest accumulation of microspheres found in viable tumor tissue. The three consecutive studies (II-IV) focused on the absorbed dose to the red marrow after PRRT. Since terbium-161, a radionuclide with a considerable emission of low-energy electrons, may be better suited to treat disseminated disease than lutetium-177 and yttrium-90, the second study focused on using an existing model of the bone marrow to investigate potential implications of bone marrow irradiation from terbium-161. The results demonstrated a strong dependence on the source distribution for terbium-161 due to the short range of the low-energy electrons while simultaneously indicating an increased absorbed dose to the red marrow compared to lutetium-177. The third study investigated the presence of somatostatin receptor subtype 2 (SSTR2) on CD34+ stem and progenitor cells in the bone marrow. After the first treatment cycle with [177Lu]Lu-DOTATATE, four SPECT/CT images were acquired for 17 patients with neuroendocrine neoplasms. The T9-L5 vertebrae, hip bones, thoracic aorta, and subcutaneous adipose tissue, along with a single tumor, were delineated in each patient. A compartment model was used to separate the contribution from blood-based activity and demonstrated prolonged retention in the bone marrow cavities for all patients and skeletal sites. These results inspired the development of a small-scale dosimetry model of the bone marrow in the fourth study to investigate how CD34+ stem and progenitor cells are irradiated by uptake related to the expression of SSTR2. The model utilized previously described spatial distributions of CD34+ stem and progenitor cells to demonstrate an increased absorbed dose from terbium-161 compared to lutetium-177. In conclusion, our results help to explain the observed hematological toxicities after [177Lu]Lu-DOTATATE therapy by demonstrating a specific uptake in the radiosensitive bone marrow. As upcoming clinical trials with terbium-161 may result in a shift from lutetium-177 in somatostatin receptor-based radionuclide therapies, we used these findings to show that this can lead to increased irradiation of the red marrow.
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| 9. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [177Lu]Lu-DOTATATE Treatment.
- 2023
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 1535-5667. ; 64:9, s. 1456-1462
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow suppression is a common side effect after [177Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive red marrow region where these cells are located. This study aimed to identify and quantify specific red marrow uptake using SPECT/CT images collected after the first treatment cycle. Methods: Seventeen patients diagnosed with neuroendocrine neoplasms were treated with [177Lu]Lu-DOTATATE. Seven of them had confirmed bone metastases. After the first treatment cycle, each patient went through 4 SPECT/CT imaging sessions 4, 24, 48, and 168h after administration. Monte Carlo-based reconstructions were used to quantify activity concentrations in tumors and multiple skeletal sites presumed to house red marrow: the T9-L5 vertebrae and the ilium portion of the hip bones. The activity concentration from the descending aorta was used as input in a compartment model intended to establish a pure red marrow biodistribution by separating the nonspecific blood-based contribution from the specific activity concentration in red marrow. The biodistributions from the compartment model were used to perform red marrow dosimetry at each skeletal site. Results: Increased uptake of [177Lu]Lu-DOTATATE was observed in the T9-L5 vertebrae and hip bones in all 17 patients compared with activity concentrations in the aorta. The mean specific red marrow uptake was 49% (range, 0%-93%) higher than the nonspecific uptake. The median (±SD) total absorbed dose to the red marrow was 0.056±0.023Gy/GBq and 0.043±0.022Gy/GBq for the mean of all vertebrae and hip bones, respectively. The patients with bone metastases had an absorbed dose of 0.085±0.046Gy/GBq and 0.069±0.033Gy/GBq for the vertebrae and hip bones, respectively. The red marrow elimination phase was statistically slower in patients with fast tumor elimination, which is in line with transferrin transport of 177Lu back to the red marrow. Conclusion: Our results suggest that specific red marrow uptake of [177Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2-expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow.
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| 10. |
- Magnander, Tobias, et al.
(författare)
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A fast GPU code for full Monte Carlo based SPECT reconstruction
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To improve image quality in SPECT/CT reconstructions, various approximate recovery resolution techniques have been developed and implemented in clinical practice. However, optimal image reconstruction requires accounting for all physical interactions of the emitted photons in the individual patient. The objectives for this study were to develop a novel Monte Carlo (MC) code for fast simulation of individual image projections, and to implement these projections in ordered subset expectation maximum (OSEM) reconstructions of SPECT/CTimages.Method: The MC code was written in Compute Unified Device Architecture language for a computer with four graphic processing units (GeForce GTX Titan X, Nvidia, USA). This enables simulations of parallel photon emission from the voxels matrix (1283 or 2563). Each CT number was converted to attenuation coefficients for photo absorption, coherent scattering and incoherent scattering. The type of interaction was determined by the ratio of attenuation coefficients in the CT voxels. For photon scattering the deflection angle was determined by the differential scattering cross sections. The accepted angle for photon interaction with the crystal was determined from the diameter and height of the collimator hole. Predefined energy and spatial resolution kernels for the crystal were used. TheMCcode was implemented intoOSEMreconstruction of 177Lu, 111In and 99mTc SPECT/CT images. The National Electrical Manufacturers Association (NEMA) image quality phantom was used to evaluate the performance of the MC reconstruction in comparison with clinical standard OSEM reconstructions and clinical state-of-the-art OSEM reconstructions with recovery resolution corrections. Results and conclusion: The performance of the MC code was 500 millions photons/s. The required number of photons emitted per voxel for obtaining low noise in the simulated image was 400 for a 1283 voxel matrix. With this number of emitted photons/voxel the MC-based OSEM reconstruction with 10 subsets was performed within 60 s/iteration. The images converged after 2-4 iterations, depending on the sphere sizes in the NEMAphantom. Thereby, the reconstruction time was <4 minutes. The contrast-to-noise level was slightly improved with increased number of emitted photons/voxel, and the reconstruction time was linearly depending on the number of emitted photons/voxel. The signal-to-background for the spheres in the NEMA phantom was clearly improved with MC-based OSEM reconstruction: e.g. for 177Lu the improvement was 37% compared to standard OSEM and 20 % compared to state-of-the-art OSEM. Furthermore, visual inspection of clinical investigations revealed clearly improved resolution and contrast with MC-based reconstruction.
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| 11. |
- Rydén, Tobias, et al.
(författare)
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Fast GPU-based Monte Carlo code for SPECT/CT reconstructions generates improved Lu-177 images
- 2018
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Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Full Monte Carlo (MC)-based SPECT reconstructions have a strong potential for correcting for image degrading factors, but the reconstruction times are long. The objective of this study was to develop a highly parallel Monte Carlo code for fast, ordered subset expectation maximum (OSEM) reconstructions of SPECT/CT images. The MC code was written in the Compute Unified Device Architecture language for a computer with four graphics processing units (GPUs) (GeForce GTX Titan X, Nvidia, USA). This enabled simulations of parallel photon emissions from the voxels matrix (1283 or 2563). Each computed tomography (CT) number was converted to attenuation coefficients for photo absorption, coherent scattering, and incoherent scattering. For photon scattering, the deflection angle was determined by the differential scattering cross sections. An angular response function was developed and used to model the accepted angles for photon interaction with the crystal, and a detector scattering kernel was used for modeling the photon scattering in the detector. Predefined energy and spatial resolution kernels for the crystal were used. The MC code was implemented in the OSEM reconstruction of clinical and phantom Lu-177 SPECT/CT images. The Jaszczak image quality phantom was used to evaluate the performance of the MC reconstruction in comparison with attenuated corrected (AC) OSEM reconstructions and attenuated corrected OSEM reconstructions with resolution recovery corrections (RRC). Result: The performance of the MC code was 3200 million photons/s. The required number of photons emitted per voxel to obtain a sufficiently low noise level in the simulated image was 200 for a 1283 voxel matrix. With this number of emitted photons/ voxel, the MC-based OSEM reconstruction with ten subsets was performed within 20 s/iteration. The images converged after around six iterations. Therefore, the reconstruction time was around 3 min. The activity recovery for the spheres in the Jaszczak phantom was clearly improved with MC-based OSEM reconstruction, e.g., the activity recovery was 88% for the largest sphere, while it was 66% for AC-OSEM and 79% for RRC-OSEM. Conclusion: The GPU-based MC code generated an MC-based SPECT/CT reconstruction within a few minutes, and reconstructed patient images of Lu-177-DOTATATE treatments revealed clearly improved resolution and contrast.
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| 12. |
- Svensson, Johanna, et al.
(författare)
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A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity.
- 2016
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Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- (177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2GBq (3.5-8.3GBq) of (177)Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period.The mean absorbed dose to the bone marrow was estimated to 0.20Gy (0.11-0.37Gy) per 7.4GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p=0.01), WBC (p<0.01) and PLT (p<0.01) counts. The total mean absorbed dose to the bone marrow was 0.64Gy (0.30-1.5Gy) per 24GBq (8.2-37GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p<0.01), WBC (p=0.01) and PLT (p<0.01) counts.The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling.
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