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1.
  • Ezzat, Kariem, et al. (författare)
  • The viral protein corona directs viral pathogenesis and amyloid aggregation
  • 2019
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta-peptide (A beta(42)), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
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2.
  • Andersson, Charlotte, et al. (författare)
  • Biodistribution of I-131 in mice is influenced by circadian variations
  • 2020
  • Ingår i: Scientific Reports. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of I-131 injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq I-131 at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of I-131 in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.
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5.
  • Andersson, Charlotte, et al. (författare)
  • Diurnal variations in biodistribution of the radionuclide I-131 in mice
  • 2016
  • Ingår i: Swedish Cancer Research Meeting, Gothenburg, 2016, November 7-8.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background: Radionuclides are routinely used to diagnose and treat many different types of cancer. I-131 is a well-established radioisotope used in e.g. treatment of thyroid cancer and neuroblastoma. Accurate knowledge of I-131 biodistribution is essential to correctly estimate the absorbed dose to normal organs and determine potential risks from I-131 exposure, which is especially important when treating children. Many biological functions in living organisms follow a circadian rhythm. Nevertheless, little is known about diurnal variations in radionuclide biodistribution. This study investigates if circadian rhythm affects I-131 biodistribution in mice and absorbed dose to organs and tissues. Materials & Methods: The radioactivity concentration in mice tissues was studied at different time-points after administration of I-131, and absorbed doses were calculated. The effect of circadian rhythm was studied by varying the time of administration. Results: Difference in activity concentration between the administration time-points was observed at many time-points after administration for most investigated tissues. For some organs differences were also observed in the absorbed dose. The highest activity concentration and absorbed dose were found in the thyroid regardless of time of administration. Conclusion: The results demonstrate that the biodistribution of I-131 in mice is influenced by the time of day of administration. These findings advocate that circadian rhythm should be considered in biodistribution studies and suggests that time-point of administration of radiopharmaceuticals containing I-131 for therapy can be further optimized. An optimized time-point could result in higher absorbed dose to the tumor and/or lower absorbed dose to normal tissues.
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6.
  • Andersson, Charlotte, et al. (författare)
  • Diurnal variations in biodistribution of the radionuclide I-131 in mice
  • 2016
  • Ingår i: Swedish Cancer Fund's planning group for oncological radionuclide therapy, Uppsala, Sweden, Nov 24-25, 2016.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background: Radionuclides are routinely used to diagnose and treat many different types of cancer. I-131 is a well-established radioisotope used in e.g. treatment of thyroid cancer and neuroblastoma. Accurate knowledge of I-131 biodistribution is essential to correctly estimate the absorbed dose to normal organs and determine potential risks from I-131 exposure, which is especially important when treating children. Many biological functions in living organisms follow a circadian rhythm. Nevertheless, little is known about diurnal variations in radionuclide biodistribution. This study investigates if circadian rhythm affects I-131 biodistribution in mice and absorbed dose to organs and tissues. Materials & Methods: The radioactivity concentration in mice tissues was studied at different time-points after administration of I-131, and absorbed doses were calculated. The effect of circadian rhythm was studied by varying the time of administration. Results: Difference in activity concentration between the administration time-points was observed at many time-points after administration for most investigated tissues. For some organs differences were also observed in the absorbed dose. The highest activity concentration and absorbed dose were found in the thyroid regardless of time of administration. Conclusion: The results demonstrate that the biodistribution of I-131 in mice is influenced by the time of day of administration. These findings advocate that circadian rhythm should be considered in biodistribution studies and suggests that time-point of administration of radiopharmaceuticals containing I-131 for therapy can be further optimized. An optimized time-point could result in higher absorbed dose to the tumor and/or lower absorbed dose to normal tissues.
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7.
  • Andersson, Charlotte, et al. (författare)
  • The influence of circadian rhythm on the biodistribution of I-131
  • 2016
  • Ingår i: Swedish Radiation Research Association for Young Scientists Workshop, Stockholm, 2016, August 25-26.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background: I-131 is well-established in nuclear medicine. The thyroid is a target organ when treating thyroid cancer with unbound I-131, but also a risk organ in I-131-based radionuclide therapy. Exposure to I-131 can also occur from the environment at nuclear accidents. Accurate knowledge of I-131 biodistribution is essential to correctly estimate the absorbed dose to organs and determine potential risks from both medical and hazard exposure. Many biological functions follow a circadian rhythm. Nevertheless, circadian rhythm remains an unknown factor in radionuclide biodistribution. Aim: The purpose of this study was to investigate if circadian rhythm affects I-131 biodistribution in mice and hence absorbed dose to mouse tissues. Methods: The radioactivity concentration in various tissues was studied at different time points after administration of I-131 and absorbed doses were calculated according to the MIRD formalism. The effect of circadian rhythm was studied by varying the time of administration. Male C57BL/6N mice were i.v. injected with I-131 at 8 am, 12 pm or 4 pm and killed after 1h to 7d. Results: Statistically significant difference in activity concentration and absorbed dose between the three injection series was observed for at least one time point after injection for many tissues. Highest activity concentration and absorbed dose were found in the thyroid. Conclusion: The results demonstrated that the biodistribution of I-131 in mice is influenced by the time of day of administration to a certain extent. These findings advocate that circadian rhythm should be considered in biodistribution studies and dose calculations.
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8.
  • Dalmo, Johanna, et al. (författare)
  • Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2.
  • 2012
  • Ingår i: Oncology reports. - 1791-2431. ; 27:1, s. 174-181
  • Tidskriftsartikel (refereegranskat)abstract
    • To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177Lu-octreotate and 111In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177Lu-octreotate or 111In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111In-MG0. Animals were sacrificed 1-7 days after injection in the 177Lu-octreotate study and 1 h after injection of 111In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177Lu were calculated. There was a specific tumor uptake of either 177Lu-octreotate or 111In-MG0. 177Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.
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