| 1. |
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| 2. |
- Forrer, Flavio, et al.
(författare)
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Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC.
- 2005
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 46:8, s. 1310-6
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Tidskriftsartikel (refereegranskat)abstract
- Therapy with [(90)Y-DOTA(0), Tyr(3)]-octreotide (DOTATOC, where DOTA = tetraazacyclododecane tetraacetic acid and TOC = D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) is established for the treatment of metastatic neuroendocrine tumors. Nevertheless, many patients experience disease relapse, and further treatment may cause renal failure. Trials with (177)Lu-labeled somatostatin analogs showed less nephrotoxicity. We initiated a prospective study with (177)Lu-DOTATOC in patients with relapsed neuroendocrine tumors after (90)Y-DOTATOC treatment. METHODS: Twenty-seven patients, pretreated with (90)Y-DOTATOC, were included. The mean time between the last treatment with (90)Y-DOTATOC and (177)Lu-DOTATOC was 15.4 +/- 7.8 mo (SD). All patients were injected with 7,400 MBq of (177)Lu-DOTATOC. Restaging was performed after 8-12 wk. Hematotoxicity or renal toxicity of World Health Organization grade 1 or 2 was not an exclusion criterion. RESULTS: Creatinine levels increased significantly, from 66 +/- 14 micromol/L to 100 +/- 44 micromol/L (P < 0.0001), after (90)Y-DOTATOC therapy. The mean hemoglobin level dropped from 131 +/- 14 to 117 +/- 13 g/L (P < 0.0001) after (90)Y-DOTATOC therapy. (177)Lu-DOTATOC therapy was well tolerated. No serious adverse events occurred. The mean absorbed doses were 413 +/- 159 mGy for the whole body, 3.1 +/- 1.5 Gy for the kidneys, and 61 +/- 5 mGy for the red marrow. After restaging, we found a partial remission in 2 patients, a minor response in 5 patients, stable disease in 12 patients, and progressive disease in 8 patients. Mean hemoglobin and creatinine levels did not change significantly. CONCLUSION: (177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.
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| 3. |
- Kneifel, Stefan, et al.
(författare)
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Individual voxelwise dosimetry of targeted (90)Y-labelled substance P radiotherapy for malignant gliomas.
- 2007
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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
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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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| 4. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Comparison of electron dose-point kernels in water generated by the Monte Carlo codes, PENELOPE, GEANT4, MCNPX, and ETRAN.
- 2009
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:4, s. 461-7
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Tidskriftsartikel (refereegranskat)abstract
- Point kernels describe the energy deposited at a certain distance from an isotropic point source and are useful for nuclear medicine dosimetry. They can be used for absorbed-dose calculations for sources of various shapes and are also a useful tool when comparing different Monte Carlo (MC) codes. The aim of this study was to compare point kernels calculated by using the mixed MC code, PENELOPE (v. 2006), with point kernels calculated by using the condensed-history MC codes, ETRAN, GEANT4 (v. 8.2), and MCNPX (v. 2.5.0). Point kernels for electrons with initial energies of 10, 100, 500, and 1 MeV were simulated with PENELOPE. Spherical shells were placed around an isotropic point source at distances from 0 to 1.2 times the continuous-slowing-down-approximation range (R(CSDA)). Detailed (event-by-event) simulations were performed for electrons with initial energies of less than 1 MeV. For 1-MeV electrons, multiple scattering was included for energy losses less than 10 keV. Energy losses greater than 10 keV were simulated in a detailed way. The point kernels generated were used to calculate cellular S-values for monoenergetic electron sources. The point kernels obtained by using PENELOPE and ETRAN were also used to calculate cellular S-values for the high-energy beta-emitter, 90Y, the medium-energy beta-emitter, 177Lu, and the low-energy electron emitter, 103mRh. These S-values were also compared with the Medical Internal Radiation Dose (MIRD) cellular S-values. The greatest differences between the point kernels (mean difference calculated for distances, <0.9 r/R(CSDA)), using PENELOPE and those from ETRAN, GEANT4, and MCNPX, were 3.6%, 6.2%, and 14%, respectively. The greatest difference between the cellular S-values for monoenergetic electrons was 1.4%, 2.5%, and 6.9% for ETRAN, GEANT4, and MCNPX, respectively, compared to PENELOPE, if omitting the S-values when the activity was distributed on the cell surface for 10-keV electrons. The largest difference between the cellular S-values for the radionuclides, between PENELOPE and ETRAN, was seen for 177Lu (1.2%). There were large differences between the MIRD cellular S-values and those obtained from PENELOPE: up to 420% for monoenergetic electrons and <22% for the radionuclides, with the largest difference for 103mRh. In conclusion, differences were found between the point kernels generated by different MC codes, but these differences decreased when cellular S-values were calculated, and decreased even further when the energy spectra of the radionuclides were taken into consideration.
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| 5. |
- 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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| 6. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production.
- 2006
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 47:5, s. 807-14
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Tidskriftsartikel (refereegranskat)abstract
- All lanthanides have similar chemical properties regarding labeling. Therefore, radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu, might easily be replaced with other radiolanthanides. The aim of this work was to investigate the suitability of electron- and positron-emitting radiolanthanides for radionuclide therapy with reference to dosimetry and production possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable or long-lived daughters, and limited photon emission were selected. The ratio of the absorbed dose rate to the tumors and the normal tissue (TND) was calculated for different tumor sizes and compared with the TND values for (90)Y and (131)I. The normal tissue and tumors were simulated as an ellipsoid and spheres, respectively. The TND values depend on the physical parameters of the radionuclides, the tumor size, and the ratio between the activity concentrations in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er, (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that can be produced no-carrier-added (nca) and with high specific activities. The Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors weighing less than 1 mg and can be produced nca and with high specific activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu had higher TND values than did (90)Y for all tumor sizes studied, but only (149)Pm can be produced nca and at high specific activities. The other electron-emitting radiolanthanides and the positron-emitting radiolanthanides showed low TND values for all tumor sizes because of the high photon contribution. CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might not be suitable for systemic radionuclide therapy (intravenous injection) because of its short half-life but might be suitable for local therapy (e.g., in body cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be suitable for radionuclide therapy.
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| 7. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Translation of dosimetric results of preclinical radionuclide therapy to clinical situations: influence of photon irradiation.
- 2007
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:2, s. 268-74
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Tidskriftsartikel (refereegranskat)abstract
- The radionuclide evaluation for therapy starts with preclinical studies in, for example, mice and rats, and various radionuclides have shown promising results. However, many radionuclides emit photons that will irradiate normal tissues. The risk of normal tissue toxicity in patients (e.g., bone marrow suppression) may be underestimated when relying on preclinical results. To illustrate the influence of photons in preclinical and clinical trials, the ratio between the tumor-to-normal tissue absorbed-dose rate ratio (TND) was calculated for humans, rats, and mice for 111In, 125I, 67Ga, 90Y, 131I, and 177Lu. The normal tissues were simulated by 70-kg, 300-g, and 20-g ellipsoids for humans, rats, and mice, respectively. It was assumed that the radionuclides were uniformly distributed, and that the activity concentration was 25 times higher in the tumor than in the normal tissue. There were only small differences between the TND values for the different species for 90Y and 177Lu. 131I showed similar TND values for rats and mice, whereas they were lower for humans. For 111In, 125I, and 67Ga, however, there were large differences between the different species. The influence of photons may thus be much lower in preclinical studies than in clinical situations. Therefore, translations of absorbed doses from animals to humans must be performed with caution.
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| 8. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Tumour control probability (TCP) for non-uniform activity distribution in radionuclide therapy.
- 2008
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Ingår i: Physics in medicine and biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 53:16, s. 4369-81
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Tidskriftsartikel (refereegranskat)abstract
- Non-uniform radionuclide distribution in tumours will lead to a non-uniform absorbed dose. The aim of this study was to investigate how tumour control probability (TCP) depends on the radionuclide distribution in the tumour, both macroscopically and at the subcellular level. The absorbed dose in the cell nuclei of tumours was calculated for (90)Y, (177)Lu, (103m)Rh and (211)At. The radionuclides were uniformly distributed within the subcellular compartment and they were uniformly, normally or log-normally distributed among the cells in the tumour. When all cells contain the same amount of activity, the cumulated activities required for TCP = 0.99 ((approximate)A(TCP=0.99)) were 1.5-2 and 2-3 times higher when the activity was distributed on the cell membrane compared to in the cell nucleus for (103m)Rh and (211)At, respectively. TCP for (90)Y was not affected by different radionuclide distributions, whereas for (177)Lu, it was slightly affected when the radionuclide was in the nucleus. TCP for (103m)Rh and (211)At were affected by different radionuclide distributions to a great extent when the radionuclides were in the cell nucleus and to lesser extents when the radionuclides were distributed on the cell membrane or in the cytoplasm. When the activity was distributed in the nucleus, (approximate)A(TCP=0.99) increased when the activity distribution became more heterogeneous for (103m)Rh and (211)At, and the increase was large when the activity was normally distributed compared to log-normally distributed. When the activity was distributed on the cell membrane, (approximate)A(TCP=0.99) was not affected for (103m)Rh and (211)At when the activity distribution became more heterogeneous. (approximate)A(TCP=0.99) for (90)Y and (177)Lu were not affected by different activity distributions, neither macroscopic nor subcellular.
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