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| 2. |
- Gugushvili, Shota, et al.
(författare)
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Nonparametric Bayesian volatility estimation
- 2019
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Ingår i: 2017 MATRIX Annals. - Cham : Springer International Publishing. - 9783030041601 ; , s. 279-302
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Haller, Stephanie, et al.
(författare)
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Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of (161)Tb-folate and (177)Lu-folate.
- 2016
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Ingår i: EJNMMI research. - : Springer Science and Business Media LLC. - 2191-219X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The radiolanthanide (161)Tb has, in recent years, attracted increasing interest due to its favorable characteristics for medical application. (161)Tb exhibits similar properties to the widely-used therapeutic radionuclide (177)Lu. In contrast to (177)Lu, (161)Tb yields a significant number of short-ranging Auger/conversion electrons (≤50keV) during its decay process. (161)Tb has been shown to be more effective for tumor therapy than (177)Lu if applied using the same activity. The purpose of this study was to investigate long-term damage to the kidneys after application of (161)Tb-folate and compare it to the renal effects caused by (177)Lu-folate.
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| 4. |
- Muller, C., et al.
(författare)
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Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute
- 2019
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using Lu-177-folate and Lu-177-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by beta over bar -particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
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| 5. |
- Muller, C., et al.
(författare)
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Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:9, s. 1919-1930
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate Tb-161 (T-1/2=6.89days; E beta(?)(av)=154keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to Lu-177-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.Methods(161)Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100MBq/nmol. Tb-161-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for Lu-177-PSMA-617. The effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. Tb-161-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.Results(161)Tb-PSMA-617 and Lu-177-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to Tb-161-PSMA-617 as compared to the effect obtained with the same activities of Lu-177-PSMA-617 over the whole investigated concentration range. Treatment of mice with Tb-161-PSMA-617 (5.0MBq/mouse and 10MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65days) compared to untreated control animals (19days). Therapy studies to compare the effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 indicated the anticipated superiority of Tb-161 over Lu-177.Conclusion(161)Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to Lu-177-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of Tb-161. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of Tb-161-PSMA-617 for the treatment of mCRPC.
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| 6. |
- Siwowska, K., et al.
(författare)
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Therapeutic Potential of Sc-47 in Comparison to Lu-177 and Y-90: Preclinical Investigations
- 2019
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Targeted radionuclide therapy with Lu-177- and Y-90-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. Sc-47 is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy beta(-)particles. In this study, Sc-47 was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of Lu-17-folate and Y-90-folate, respectively. In vitro, Sc-47-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to Lu-177-folate, but Y-90-folate was more potent at equal activities due to the higher energy of emitted beta(-)particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (similar to 21 Gy) when treated with Sc-47-folate (12.5 MBq), Lu-177-folate (10 MBq), and Y-90-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, Sc-47 is likely to be comparable to Lu-177 when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with Sc-44 or Sc-43 as a diagnostic match, enabling the realization of radiotheragnostics in future.
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| 7. |
- Umbricht, C. A., et al.
(författare)
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Alpha-PET for Prostate Cancer: Preclinical investigation using Tb-149-PSMA-617
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- In this study, it was aimed to investigate Tb-149-PSMA-617 for targeted a-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. Tb-149-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. Tb-149-PSMA-617 was applied at 1 x 6 MBq (Day 0) or 2 x 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 x 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the beta(+)-emission of Tb-149, tumor localization was feasible using PET/CT after injection of Tb-149-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of Tb-149-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of Tb-149 for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand's tissue distribution.
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