| 61. |
- Montelius, Mikael, 1979, et al.
(författare)
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Multiparametric MR for non-invasive evaluation of tumour tissue histological characteristics after radionuclide therapy.
- 2019
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Ingår i: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- Early non-invasive tumour therapy response assessment requires methods sensitive to biological and physiological tumour characteristics. The aim of this study was to find and evaluate magnetic resonance imaging (MRI) derived tumour tissue parameters that correlate with histological parameters and that reflect effects of radionuclide therapy. Mice bearing a subcutaneous human small-intestine neuroendocrine tumour were i.v. injected with 177 Lu-octreotate. MRI was performed (7T Bruker Biospec) on different post-therapy intervals (1 and 13days) using T2-weighted imaging, mapping of T2* and T1 relaxation time constants, as well as diffusion and dynamic contrast enhancement (DCE-MRI) techniques. After MRI, animals were killed and tumours excised. Four differently stained histological sections of the most central imaged tumour plane were digitized, and segmentation techniques were used to produce maps reflecting fibrotic and vascular density, apoptosis, and proliferation. Histological maps were aligned with MRI-derived parametric maps using landmark-based registration. Correlations and predictive power were evaluated using linear mixed-effects models and cross-validation, respectively. Several MR parameters showed statistically significant correlations with histological parameters. In particular, three DCE-MRI-derived parameters reflecting capillary function additionally showed high predictive power regarding apoptosis (2/3) and proliferation (1/3). T1 could be used to predict vascular density, and perfusion fraction derived from diffusion MRI could predict fibrotic density, although with lower predictive power. This work demonstrates the potential to use multiparametric MRI to retrieve important information on the tumour microenvironment after radiotherapy. The non-invasiveness of the method also allows longitudinal tumour tissue characterization. Further investigation is warranted to evaluate the parameters highlighted in this study longitudinally, in larger studies, and with additional histological methods.
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| 62. |
- Montelius, Mikael, 1979, et al.
(författare)
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Multiparametric MRI (mpMRI) for spatiotemporal characterization of tumor tissue response to radionuclide treatment
- 2016
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Ingår i: 62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016.
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Konferensbidrag (refereegranskat)abstract
- Background: Development and optimization of efficient tumor treatment methods are needed. Increased understanding of the complex and heterogeneous tumor microenvironment in response to treatment is thus required, necessitating multiple, non-invasive biomarker acquisition with spatiotemporal resolution. mpMRI potentially offers methods with the required capabilities. Aim: To assess the possibility to non-invasively retrieve multiple, complementary information on radionuclide treatment effects on tumor microenvironment, using spatiotemporally resolved mpMRI. Methods: 19 mice with neuroendocrine tumors (~1 cm) received 15 MBq 177Lu-octreotate i.v. on day 0 (tumor dose ~4 Gy) and were imaged on day -1, 1, 3, 8 and 13. Imaging included IVIM (reflecting apoptosis/necrosis (AN) and capillary activity (CA)) [1], T1/T2* mapping (microstructural alterations (MA) and hypoxia/hemorrhage (HH)), DCE (microvessel integrity/perfusion tracer kinetics (IK)) and T2w MRI (morphology/size). Matlab based post-processing included voxelwise model fitting and tumor delineation to define a binary mask for volumetry and parameter extraction. An automatic separation of the mask into annular disks of preserved tumor shape but stepwise decreased size was performed, allowing separate regional analyses of central to peripheral parts of the tumor. Results: Groups with high/low response (HRG n = 8/LRG n = 4), based on post-treatment tumor volume (monotonically decreasing/increasing days 1-13) were identified. Post-treatment changes with significant separation of HRG from LRG (p < 0.05) were found in parameters related to AN: 1‡ parameter, CA: 1‡, HH: 1, IK: 10 (3†, 7‡) and MA: 1. Pre-treatment HRG/LRG prediction was possible in all 15 (8†) parameters; AN: 1, CA: 1, HH: 1, IK: 11 (8†) and MA: 1. (†Only after spatial separation. ‡Only transiently). Conclusions: Multiple, complementary biomarker information related to radionuclide tumor treatment could be extracted using spatiotemporally resolved mpMRI. Several parameters required separate analysis of sub-tumoural regions in order to separate high from low responding tumors, and some were only transiently affected, highlighting the importance of repeated measurements with spatially resolved techniques. References: 1.Le Bihan et al. Radiology, 1988
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| 63. |
- Montelius, Mikael, 1979, et al.
(författare)
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Multiparametric MRI with spatiotemporal evaluation reveals potential therapy response biomarkers for 177Lu-octreotate therapy of mice with human neuroendocrine tumor
- 2017
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Ingår i: ISMRM 25th Annual Meeting. 22-27 April 2017, Honolulu, Hawaii, USA.
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Konferensbidrag (refereegranskat)abstract
- Tissue parameters derived from multiparametric MRI were evaluated as potential imaging biomarkers for therapy response assessment in mice with human neuroendocrine tumor treated with 177Lu-octreotate. Animals were imaged before and repeatedly after 177Lu-octreotate treatment, using T2w, IVIM-DWI, DCE-MRI, T1- and T2*-mapping techniques. MR-parameters were evaluated regionally and longitudinally, and quantitative proteomics was used to evaluate underlying biological response in central and peripheral tumor separately. Several MR-parameters showed strong correlation with tumor response, as verified by MRI-based tumor volume measurements, but also with proteins associated with radiobiological effects on tumor tissue. Spatial and temporal evaluation increased sensitivity of the methods.
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| 64. |
- Nordlund, Per-Johan, et al.
(författare)
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A Framework for Particle Filtering for Positioning, Navigation and Tracking
- 2001
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Ingår i: Proceedings of the 11th IEEE Signal Processing Workshop on Statistical Signal Processing. - : IEEE. - 0780370112 ; , s. 34-37
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Konferensbidrag (refereegranskat)abstract
- A framework for positioning, navigation and tracking problems using particle filters (recursive Monte Carlo methods) is developed. Automotive and airborne applications, approached in this framework, have proven a numerical advantage over classical Kalman filter based algorithms. Here the use of non-linear measurement models and non-Gaussian measurement noise is the main explanation for the improvement in accuracy, and models for relevant sensors are surveyed.
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| 65. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Proteomic analysis of normal mouse thyroids after 131I administration
- 2015
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Ingår i: 15th International Congress of Radiation Research, Kyoto, Japan, May 25-29.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Iodine is essential for the normal function of the thyroid gland, which in turn is susceptible to cellular damage after treatment with the β-emitter radioiodine (131I). Individuals exposed to 131I at a young age via contaminated food or nuclear crises such as the Chernobyl nuclear accident are at greater risk of developing e.g. thyroid cancer and other thyroid disorders later on in life. These factors may therefore have clinical implications for patients receiving 131I-based radionuclide therapy. The aim of this study was to identify potential biomarkers in normal thyroid tissue that are induced by 131I administration. Non-tumor-bearing female Balb/c nude mice were i.v. injected with 490 kBq 131I or physiological saline and killed 24 h after injection. The mean absorbed dose to the thyroid was calculated to 32 Gy. Protein lysates were extracted from surgically excised thyroids and analyzed using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-dependent protein identification and relative quantification. The LC-MS/MS analysis identified 17 differentially expressed proteins (p<0.05), of which 13 showed down-regulation in the 131I-treated group compared to the controls. There was an enrichment of proteins associated with hypoxia/ischemia, oxygen transport/erythrocyte development, regulation of cell cycle, and metabolism. Interestingly, Hypoxia up-regulated protein 1 (HYOU1), known to be up-regulated during hypoxic conditions, was up-regulated in treated samples. In addition, five proteins associated with oxygen transport/erythrocyte development were identified, all of which were down-regulated, i.e. Bisphosphoglycerate mutase (PMGE), Ankyrin-1 (ANK1), and Hemoglobin subunits beta-1 (HBB1), beta-2 (HBB2), alpha (HBA). Taken together, these findings suggest the presence of hypoxic conditions and reduced oxygen transport in normal mouse thyroids 24 h after 131I administration. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.
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| 66. |
- Romiani, Arman, 1991, et al.
(författare)
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Better therapeutic results after fractionated administration of Lu-177-octreotate in mice bearing human neuroblastoma
- 2018
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Ingår i: The European Association of Nuclear Medicine (EANM).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neuroblastoma (NB) is a neuroendocrine tumor and one of the most common cancer types in infants. NB is a heterogeneous cancer form, meaning that it has various characteristics and features, with diverse outcomes. High-risk NB has a 5-year survival rate of only 40-50%, demonstrating the need for new and improved treatment options for this patient group. Since NB overexpresses somatostatin receptors Lu-177-octreotate has the potential to be a treatment option. Our previous in vitro studies indicated high and specific uptake of Lu-177-octreotate in the human NB cell lines CLB-Bar and IMR-32. Furthermore, biodistribution studies of Lu-177-octreotate in NB-xenografted mice showed high uptake in tumor tissue in comparison with risk organs. These promising results encouraged studies on the anti-tumor effects of Lu-177-octreotate therapy. The aim of this work was to study the anti-tumor effects after fractionated administration of Lu-177-octreotate in nude mice bearing CLB-Bar. Methods: Nude BALB/c mice aged 5-6 weeks were injected with 2x10^6 CLB-Bar cells on the flank of the mice. Mice with tumors between 250 and 1100 mm^3 were included in the study. Three groups of mice were i.v injected with totally 15 MBq Lu-177-octreotate: given as 15 MBq x1, 7.5 MBq x2 with a 2-h interval or 5 MBq x3 with 1-h interval. The tumor volume was measured with a caliper twice a week after injection and the mice were killed when the tumor mass exceeded 10 % of the body weight. Results: The relative tumor volume 7 days post injection was 2.0, 1.7 and 1.3 for the 15 MBq x1, 7.5 MBq x2 and 5 MBq x3 group, respectively, corresponding mean survival time after study start was of 9.6, 14 and 16 days, respectively. Conclusion: The fractionated administration of Lu-177-octreotate resulted in a better anti-tumor effect, with the most prominent results from 3x5 MBq. These results might be due to saturation of the somatostatin receptors for the higher amounts of Lu-177-octreotate or upregulation of receptors from previous fractions. Further studies are needed to optimize the fractionation scheme and to evaluate the mechanisms behind the results.
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| 67. |
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| 68. |
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| 69. |
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| 70. |
- Romiani, Arman, 1991, et al.
(författare)
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Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice
- 2024
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Ingår i: Heliyon. - 2405-8440. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177Lu-octreotate and 177Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177Lu-octreotate or 177Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177Lu-octreotide compared to 177Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177Lu-octreotate, respectively. 177Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8, TNSFS10, and TRADD were regulated after administration with 177Lu-octreotate. Treatment with 177Lu-octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD, and of the anti-apoptotic gene IL10 as well as the apoptosis-related gene TNF. Conclusion: 177Lu-octreotide gave somewhat better anti-tumor effects than 177Lu-octreotate. The similar effect observed in the treated groups with 177Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.
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