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Träfflista för sökning "L773:1619 7070 OR L773:1619 7089 ;pers:(Bernhardt Peter 1966)"

Sökning: L773:1619 7070 OR L773:1619 7089 > Bernhardt Peter 1966

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2.
  • Guzik, P., et al. (författare)
  • Promising potential of Lu-177 Lu-DOTA-folate to enhance tumor response to immunotherapy-a preclinical study using a syngeneic breast cancer model
  • 2021
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:4, s. 984-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [Lu-177]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [Lu-177]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [Lu-177]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 x 200 mu g; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [Lu-177]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [Lu-177]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [Lu-177]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [Lu-177]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.
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3.
  • Hagmarker, Linn, et al. (författare)
  • Characterisation of a planar dosimetry method estimating the absorbed dose to the bone marrow during 177Lu-DOTATATE treatment
  • 2016
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
  • 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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6.
  • Hemmingsson, Jens, 1986, et al. (författare)
  • Simulation of 90Y microspheres in selective internal radiation therapy (SIRT) reveals different heterogeneity profiles for glass and resin microspheres.
  • 2016
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. 43 (Suppl 1): 1. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
  • 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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7.
  • Högberg, Jonas, 1976, et al. (författare)
  • On the dose heterogeneity in normal liver tissue due to treatment of liver tumors with yttrium-90 microspheres
  • 2012
  • Ingår i: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012. European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:suppl 2, s. S281-S281
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: When treating patients with primary or metastatic liver cancer, applying external radiotherapy, an absorbed dose of 30 - 35 Gy to the whole normal liver tissue volume is associated with a 5 % risk of radiation-induced hepatitis. If less than half of the normal liver volume is being exposed, the threshold for a 5 % risk of hepatitis is increased to above 60 Gy for both primary and metastatic liver cancer. Experience with patients treated with SIR-Spheres® (Sirtex Medical Ltd.), resin microspheres aggregated with yttrium-90, has shown that most patients tolerate an average absorbed dose to normal liver tissue higher than 60 Gy. The high tolerance for this treatment procedure can probably be explained by the resulting heterogenic distribution of radioactivity. It is of interest to study the degree of heterogeneity in the distribution of radioactivity in normal liver tissue, in order to explain or even predict the tolerance to radiation. The aim of this study was to describe the degree of heterogeneity by comparing the relative standard deviations of the radioactivity concentration for different sample mass categories. Materials and Methods: Two patients with cholangiocarcinoma were planned for a combined treatment with yttrium-90-aggregated SIR-Spheres followed by surgery 9 days after radiotherapy. According to standard protocol for treatments with SIR-Spheres, the therapies were preceded by Tc-99m-labled Macro aggregated albumin (Tc-99m-MAA) distribution studies for pre-therapeutic dosimetry and lung shunting evaluations. After surgery the resected tissue, containing both tumour and normal tissue, was studied regarding the distribution of radioactivity. Several small circular samples of normal liver tissue were punched out from 2 mm thick slices of resected tissue, deliberately varying the sizes, and thus the masses of the tissue samples (from 6 to 102 mg). The samples were weighed and categorized in two (first patient) and three (second patient) groups, depending on sample mass. After this the radioactivity was measured with a NaI(Tl) detector. The relative standard deviations (SD/Median) for the radioactivity concentration for each sample mass group were determined and compared. Results: The relative standard deviation for the radioactivity concentration was decreasing rapidly with increasing sample mass. Conclusion: The results indicate a considerable degree of heterogeneity in the distribution of microspheres. One probable explanation for this heterogeneity is clustering of microspheres in the blood vessels.
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8.
  • Kneifel, Stefan, et al. (författare)
  • Individual voxelwise dosimetry of targeted (90)Y-labelled substance P radiotherapy for malignant gliomas.
  • 2007
  • Ingår i: European journal of nuclear medicine and molecular imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 34:9, s. 1388-95
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently overexpressed in malignant gliomas. The peptidic vector (111)In/(90)Y-DOTAGA-substance P binds to these receptors and can be used for local treatment of brain tumours. Dosimetry for this interstitial brachytherapy has mainly been done using geometrical models; however, they often do not faithfully reproduce the in vivo biodistribution of radiopharmaceuticals, which is indispensable to correlate the deposited energy with clinical response. The aim of this study was to establish a reproducible dosimetry protocol for intratumoural radiopeptide therapy. METHODS: For test and therapeutic injections, 2 MBq of (111)In-substance P and 370-3,330 MBq of (90)Y-substance P, respectively, were applied in 12 patients with malignant gliomas. Over a period of 24 h, serial SPECT scans were performed on a dual-head SPECT camera. The scans were acquired in a double-energy window technique together with (99m)Tc-ECD in order to co-register the dose distributions with a separately acquired, contrast-enhanced CT scan. Quantitative voxelwise dose distribution maps (in Gy/GBq) were computed from these data using a mono-exponential decay approach. Pre- and post-therapeutic values were compared. RESULTS: Agreement between pre- and post-therapeutic dosimetry was very good and delivered absolute dose values in Gy per injected GBq. In all patients, the pretherapeutic test injection together with the CT overlay technique could predict the precise localisation of dose deposition in an anatomical context. CONCLUSION: This protocol allows a precise pretherapeutic computation of the expected three-dimensional dose distribution and is clearly superior to the previously used dosimetry based on planar scintigraphic images. It has become an indispensable tool for planning intratumoural radiopeptide therapy in glioma patients.
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9.
  • Magnander, Tobias, et al. (författare)
  • A fast GPU code for full Monte Carlo based SPECT reconstruction
  • 2016
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
  • 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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10.
  • Müller, Cristina, et al. (författare)
  • Direct in vitro and in vivo comparison of (161)Tb and (177)Lu using a tumour-targeting folate conjugate.
  • 2014
  • Ingår i: European journal of nuclear medicine and molecular imaging. - : Springer Science and Business Media LLC. - 1619-7089 .- 1619-7070. ; 41:3, s. 476-485
  • Tidskriftsartikel (refereegranskat)abstract
    • The radiolanthanide (161)Tb (T 1/2 = 6.90 days, Eβ(-) av = 154 keV) was recently proposed as a potential alternative to (177)Lu (T 1/2 = 6.71 days, Eβ(-) av = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare (161)Tb and (177)Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09).
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