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- Lagerlöf, Jakob Heydorn, 1978, et al.
(författare)
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The impact of including spatially longitudinal heterogeneities of vessel oxygen content and vascular fraction in 3D tumor oxygenation models on predicted radiation sensitivity.
- 2014
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Ingår i: Medical physics. - : Wiley. - 0094-2405 .- 2473-4209. ; 41:4
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen distribution models have been used to analyze the influences of oxygen tensions on tissue response after radiotherapy. These distributions are often generated assuming constant oxygen tension in the blood vessels. However, as red blood cells progress through the vessels, oxygen is continuously released into the plasma and the surrounding tissue, resulting in longitudinally varying oxygen levels in the blood vessels. In the present study, the authors investigated whether a tumor oxygenation model that incorporated longitudinally varying oxygen levels would provide different predictions of necrotic fractions and radiosensitivity compared to commonly used models with a constant oxygen pressure.
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| 3. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Dosimetric characterization of radionuclides for systemic tumor therapy: influence of particle range, photon emission, and subcellular distribution.
- 2006
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Ingår i: Medical physics. - : Wiley. - 0094-2405 .- 2473-4209. ; 33:9, s. 3260-9
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Tidskriftsartikel (refereegranskat)abstract
- Various radionuclides have been proposed for systemic tumor therapy. However, in most dosimetric analysis of proposed radionuclides the charged particles are taken into consideration while the potential photons are ignored. The photons will cause undesirable irradiation of normal tissue, and increase the probability of toxicity in, e.g., the bone marrow. The aim of this study was to investigate the dosimetric properties according to particle range, photon emission, and subcellular radionuclide distribution, of a selection of radionuclides used or proposed for radionuclide therapy, and to investigate the possibility of dividing radionuclides into groups according to their dosimetric properties. The absorbed dose rate to the tumors divided by the absorbed dose rate to the normal tissue (TND) was estimated for different tumor sizes in a mathematical model of the human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres of different sizes (1 ng-100 g). The radionuclides were either assumed to be uniformly distributed throughout the entire tumor and normal tissue, or located in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of the normal cells. Fifty-nine radionuclides were studied together with monoenergetic electrons, positrons, and alpha particles. The tumor and normal tissue were assumed to be of water density. The activity concentration ratio between the tumor and normal tissue was assumed to be 25. The radionuclides emitting low-energy electrons combined with a low photon contribution, and the alpha emitters showed high TND values for most tumor sizes. Electrons with higher energy gave reduced TND values for small tumors, while a higher photon contribution reduced the TND values for large tumors. Radionuclides with high photon contributions showed low TND value for all tumor sizes studied. The radionuclides studied could be divided into four main groups according to their TND values: beta emitters, Auger electron emitters, photon emitters, and alpha emitters. The TND values of the beta emitters were not affected by the subcellular distribution of the radionuclide. The TND values of the Auger electron emitters were affected by the subcellular radionuclide distribution. The photon emitters showed low TND values that were only slightly affected by the subcellular radionuclide distribution. The alpha emitters showed high TND values that were only slightly affected by the subcellular radionuclide distribution. This dosimetric characterization of radionuclides may be valuable in choosing the appropriate radionuclides for specific therapeutic applications.
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| 4. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Model of metastatic growth valuable for radionuclide therapy
- 2003
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Ingår i: Medical physics. - 0094-2405. ; 30:12, s. 3227-32
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to make a Monte Carlo simulation approach to estimate the distribution of tumor sizes and to study the curative potential of three candidate radionuclides for radionuclide therapy: the high-energy electron emitter 90Y, the medium-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. A patient with hepatocellular carcinoma with recently published serial CT data on tumor growth in the liver was used. From these data the growth of the primary tumor, and the metastatis formation rate, were estimated. Assuming the same tumor growth of the primary and all metastases and the same metastatis formation rate from both primary and metastases the metastatic size distribution was simulated for various time points. Tumor cure of the metastatic size distribution was simulated for uniform activity distribution of three radionuclides; the high-energy electron emitter 90Y, the mean-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. The simulation of a tumor cure was performed for various time points and tumor-to-normal tissue activity concentrations, TNC. It was demonstrated that it is important to start therapy as early as possible after diagnosis. It was of crucial importance to use an optimal radionuclide for therapy. These simulations demonstrated that 90Y was not suitable for systemic radionuclide therapy, due to the low absorbed fraction of the emitted electrons in small tumors (< 1 mg). If TNC was low 103mRh was slightly better than 177Lu. For high TNC values low-energy electron emitters, e.g., 103mRh was the best choice for tumor cure. However, the short half-life of 103mRh (56 min) might not be optimal for therapy. Therefore, other low-energy electron emitters, or alpha emitters, should be considered for systemic targeted therapy.
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| 5. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Modelling of metastatic cure after radionuclide therapy: influence of tumor distribution, cross-irradiation, and variable activity concentration
- 2004
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Ingår i: Medical physics. - : Wiley. - 0094-2405. ; 31:9, s. 2628-35
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the influence of tumor number and size, cross-irradiation from normal tissue, and of variable activity concentration on metastatic cure after radionuclide therapy. A model to calculate the metastatic cure probability (MCP) was developed, in which it was assumed that the tumor response was an exponential function of the absorbed dose. All calculations were performed for monoenergetic electron emitters with different energies (10-1000 keV). The influence of tumor size and number of tumors were investigated with different log uniform distributions; the basic tumor distribution consisted of tumors with 1, 10, ..., 10(11) cells. The influence of cross-irradiation was assessed by calculating MCP for various tumor-to-normal tissue activity concentration ratios (TNC). The influence of variable activity concentration between tumors was calculated by assuming that the activity concentration in tumors was an inverse power law function of tumor mass. The required activity concentration (C0.9) and absorbed dose (D0.9) to obtain MCP=0.9 was calculated in the different models. The C0.9 and D0.9 needed to obtain MCP were very high; more than 25 MBq/g and 80 Gy, respectively. The lowest C0.9 and D0.9 for equal activity concentration in the different tumor sizes were obtained for electron energies less than 80 keV. For higher energies the low absorbed energy fraction in small tumors will increase the required C0.9 and D0.9 markedly. Cross-irradiation from normal cells surrounding the tumor will cause sterilization of the smallest tumors and decrease the required C0.9 and D0.9 for higher electron energies. Assuming that the activity concentration decreased with increased tumor mass caused a marked increase in C0.9 and D0.9 in favor of higher electron energies. With the MCP model we demonstrated significant influence of the number of tumors, their size, TNC and variable activity concentration on MCP. The results are valuable when evaluating optimal choices for radionuclides for internal-emitter therapy.
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| 6. |
- Lagerlöf, Jakob Heydorn, 1978, et al.
(författare)
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3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs.
- 2011
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Ingår i: Medical physics. - : Wiley. - 0094-2405. ; 38:8, s. 4888-93
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Tidskriftsartikel (refereegranskat)abstract
- Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO2) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO2 and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO2-distribution due to antiangiogenic treatment in combination with radionuclide therapy.
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| 7. |
- Lagerlöf, Jakob Heydorn, 1978, et al.
(författare)
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Oxygen distribution in tumors: A qualitative analysis and modeling study providing a novel Monte Carlo approach
- 2014
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 41:9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To construct a Monte Carlo (MC)-based simulation model for analyzing the dependence of tumor oxygen distribution on different variables related to tumor vasculature [blood velocity, vessel-to-vessel proximity (vessel proximity), and inflowing oxygen partial pressure (pO2)]. Methods: A voxel-based tissue model containing parallel capillaries with square cross-sections (sides of 10 μm) was constructed. Green's function was used for diffusion calculations and Michaelis-Menten's kinetics to manage oxygen consumption. The model was tuned to approximately reproduce the oxygenational status of a renal carcinoma; the depth oxygenation curves (DOC) were fitted with an analytical expression to facilitate rapid MC simulations of tumor oxygen distribution. DOCs were simulated with three variables at three settings each (blood velocity, vessel proximity, and inflowing pO2), which resulted in 27 combinations of conditions. To create a model that simulated variable oxygen distributions, the oxygen tension at a specific point was randomly sampled with trilinear interpolation in the dataset from the first simulation. Six correlations between blood velocity, vessel proximity, and inflowing pO2 were hypothesized. Variable models with correlated parameters were compared to each other and to a nonvariable, DOC-based model to evaluate the differences in simulated oxygen distributions and tumor radiosensitivities for different tumor sizes. Results: For tumors with radii ranging from 5 to 30 mm, the nonvariable DOC model tended to generate normal or log-normal oxygen distributions, with a cut-off at zero. The pO2 distributions simulated with the six-variable DOC models were quite different from the distributions generated with the nonvariable DOC model; in the former case the variable models simulated oxygen distributions that were more similar to in vivo results found in the literature. For larger tumors, the oxygen distributions became truncated in the lower end, due to anoxia, but smaller tumors showed undisturbed oxygen distributions. The six different models with correlated parameters generated three classes of oxygen distributions. The first was a hypothetical, negative covariance between vessel proximity and pO2 (VPO-C scenario); the second was a hypothetical positive covariance between vessel proximity and pO2 (VPO+C scenario); and the third was the hypothesis of no correlation between vessel proximity and pO2 (UP scenario). The VPO-C scenario produced a distinctly different oxygen distribution than the two other scenarios. The shape of the VPO-C scenario was similar to that of the nonvariable DOC model, and the larger the tumor, the greater the similarity between the two models. For all simulations, the mean oxygen tension decreased and the hypoxic fraction increased with tumor size. The absorbed dose required for definitive tumor control was highest for the VPO+C scenario, followed by the UP and VPO-C scenarios. Conclusions: A novel MC algorithm was presented which simulated oxygen distributions and radiation response for various biological parameter values. The analysis showed that the VPO-C scenario generated a clearly different oxygen distribution from the VPO+C scenario; the former exhibited a lower hypoxic fraction and higher radiosensitivity. In future studies, this modeling approach might be valuable for qualitative analyses of factors that affect oxygen distribution as well as analyses of specific experimental and clinical situations.
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