51. |
- 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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52. |
- 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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53. |
- Pearce, Ruth, et al.
(författare)
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Development of FETs and resistive devices based on epitaxially grown single layer graphene on SiC for highly sensitive gas detection
- 2012
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Ingår i: Materials Science Forum Vols 717 - 720. - : Trans Tech Publications Inc.. - 9783037854198 ; , s. 687-690
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Konferensbidrag (refereegranskat)abstract
- Epitaxially grown single layer graphene on silicon carbide (SiC) resistive sensors were characterised for NO2 response at room and elevated temperatures, with an n-p type transition observed with increasing NO2 concentration for all sensors. The concentration of NO2 required to cause this transition varied for different graphene samples and is attributed to varying degrees of substrate induced Fermi-level (E-F) pinning above the Dirac point. The work function of a single layer device increased steadily with increasing NO2 concentration indicating no change in reaction mechanism for high and low concentrations despite a change in sensor response direction. Epitaxially grown graphene device preparation is challenging due to poor adhesion of the graphene layer to the substrate. A field effect transistor (FET) device is presented which does not require wire bonding to contacts on graphene.
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54. |
- 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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59. |
- Romiani, Arman, 1991, et al.
(författare)
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Neuroblastoma xenograft models demonstrate the therapeutic potential of Lu-177-octreotate
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40-50%, indicating the need for novel and improved treatment options. Lu-177-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of Lu-177-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of Lu-177-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5-7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq Lu-177-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1-5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High Lu-177 concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq Lu-177-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq Lu-177-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of Lu-177-octreotate as a therapeutic alternative for metastatic NB.
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60. |
- Romiani, Arman, 1991, et al.
(författare)
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The potential of Lu-177-octreotate as a therapeutic alternative for metastatic neuroblastoma
- 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 (övrigt vetenskapligt/konstnärligt)abstract
- Radionuclide therapy using 177Lu-octreotate is a promising treatment option for neuroendocrine tumors with overexpression of somatostatin receptors (SSTR). In order to screen and evaluate the usefulness of 177Lu-octreotate for therapy of a specific neuroendocrine tumor type, knowledge of the binding and internalization of the 177Lu-octreotate to tumor cells is needed. The aim of this study was to determine the binding and internalization of 177Lu-octreotate in three neuroblastoma (NB) cell lines and to perform biodistribution studies in animals bearing NB. Binding and internalization of 177Lu-octreotate to the human NB cell lines IMR-32 and CLB-BAR were investigated in vitro. Cell cultures were incubated with various amounts of 177Lu-octreotate with or without excess of octreotide and harvested at 24 h and 48 h after administration. The amount of 177Lu associated to the membrane and internalized into the cells were determined. IMR-32, CLB-BAR and GEMO bearing BALB/c nude mice (n=5-6/group) were i.v. injected with 15 MBq 177Lu-octreotate and killed 1 h, 24 h and 7 days after administration. Tissue samples were collected and radioactivity concentrations were determined. Tumor-to-normal-tissue ratios (T/N) were calculated and compared with previous data. The highest binding and internalization of 177Lu in vitro occurred after 48 h: 78% and 47% of the 177Lu-octreotate in IMR-32 and CLB-BAR cells, respectively. Binding and internalization was successfully blocked with octreotide, indicating a specific uptake. In the mice bearing GEMO, T/Blood and T/Kidney values 1 h after injection were 18 and 0.71, respectively, and 7 days after injection 2300 and 27, respectively. Corresponding values for IMR-32 were 7.5 and 0.40; 1300 and 7.8, 1 h and 7 d after injection, respectively. Corresponding values for CLB-BAR were 18 and 0.24; 113 and 0.94, 1 h and 7 d after injection, respectively. This study clearly shows the potential of 177Lu-octreotate as a therapeutic alternative in the treatment of metastatic NB. The T/N values for all three tumor types investigated showed high values compared with previously investigated neuroendocrine tumor types. The results are very promising, and future studies will characterize anti-tumor effects following 177Lu-octreotate therapy.
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