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Search: L773:1619 7070 > Umeå University

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  • Andersson, M., et al. (author)
  • Dynamic absorbed dose calculations to the urinary bladder wall for the ICRP compartmental models of iodide and technetium
  • 2019
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:SUPPL 1, s. S281-S282
  • Journal article (other academic/artistic)abstract
    • Aim/Introduction: The urinary bladder wall is a radiosensitive organ that can receive a high absorbed dose from radiopharmaceuticals used even in diagnostic nuclear medicine. The commonly used method to calculate the absorbed dose to the urinary bladder wall is to apply absorbed fractions or S-values derived for a static volume of the content e.g. 200 mL for adult males. However, there are some dynamic models to estimate the photon and electron absorbed dose contributions to the inner surface or the mean absorbed dose to the bladder wall. These models have only been applied on adults and use descriptive biokinetic models for the transfer of radionuclides. The aim of this work is to estimate the absorbed dose, based on Monte Carlo-simulated dynamic urinary bladders and the ICRP compartmental biokinetic models of iodide and pertechnetate. The calculations include sex specific absorbeddose and estimations for preadults of 15- 10- 5- 1-year and newborn.Materials and Methods: S-values were calculated for different volumes of the content with a fix mass of the wall. As an approximation a spherical shape was assumed. Calculations were based on anatomical and physiological data of the reference sets of values given in ICRP Publication 89. The reference values were given for both male and female subjects of six different ages: newborn, 1-, 5-, 10-, 15-years, and adult. The elemental compositions of the urinary bladder wall and content were taken from the ICRP Publication 110.Results: For adult male assuming a urinary flow rate of 1600 ml/day, an initial urine volume of 100 ml, a voiding volume at 300 ml and a residual volume of 30 ml, the cumulated activity will for intravenously administered activity of Tc-99m pertechnetate be 30 % lower than assuming a 3.5 hour voiding interwall. The absorbed dose to the urinary bladder wall will be 64% lower also applying the dynamic S-values on the dynamic case. Using the same biological parameters for intravenous intake of I-131 iodide, the cumulated activity will be 60 % higher for the dynamic case and the mean absorbed dose to the urinary bladder wall 30 % lower.Conclusion: This project aims to perform more realistic calculation of absorbed dose to the urinary bladder calculations. This is done by tracking the activity in the urinary content at each time on compartment models and applying the time dependent activity to urinary flow and Monte Carlo simulated S-values.
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  • Elgh, Eva, et al. (author)
  • Memory functions and rCBF (99m)Tc-HMPAO SPET : developing diagnostics in Alzheimer's disease
  • 2002
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 29:9, s. 1140-1148
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.
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  • Eriksson, David, et al. (author)
  • Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours.
  • 2003
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 30:6, s. 895-906
  • Journal article (peer-reviewed)abstract
    • Radiation therapy of malignant tumours can be delivered by external beam radiation (RT) or radioimmunotherapy (RIT), using nuclides attached to monoclonal antibodies (mAbs). These treatment modalities have now been combined in order to investigate putative therapeutic advantages and elucidate the biological responses involved. Nude mice were transplanted subcutaneously on the back with human HeLa Hep2 tumour cells. RT (3x5 Gy) and/or 100 microg (131)I-labelled mAb H7, against placental alkaline phosphatase, or (131)I-labelled mAb TS1, against cytokeratin, was administered separately or in combination (specific activity of 120-200 MBq/mg antibody). Significant tumour growth retardation was observed both with RT alone and with RIT alone. Combining these regimens enhanced the therapeutic effects further, and a significant reduction in tumour volume could be demonstrated. The tumours were subjected to extensive histochemical and immunohistochemical investigations in order to elucidate changes in biology and histology within them. The following stainings were used: haematoxylin-eosin (morphology), Ki67 (proliferation), M30 (apoptosis), TUNEL (apoptosis) and endoglin (vascularisation). Tumours in the control group grew fast, with an average tumour doubling time of 9 days. These tumours contained large viable tumour cell masses displaying vast proliferation zones of Ki67-positive tumour cells, as well as necrotic regions and small amounts of connective tissue. Apoptotic cells could be identified both with M30 and TUNEL staining. When RT was applied, the growth rate was significantly reduced (doubling time 19 days) and typical alterations in morphology were seen, with a relative increase in connective tissue and a decrease in necrotic regions. Apoptotic cells were identified and a decrease in cell density was also observed. When RIT alone was applied, the growth parameters indicated a longer lasting growth reduction, especially when TS1 was used separately or in combination with H7. The histological appearances of these tumours were somewhat different from the RT-treated tumours, with a larger portion of intratumoural cysts. These tumours also presented a reduced tumour cell density. Dramatic effects were observed when RT was combined with RIT, with a pronounced growth reduction seen in all combination treatment groups. Pronounced tumour volume reduction was also evident in both the RT + RIT ((131)I-TS1) group and RT + RIT ((131)I-TS1/(131)I-H7) group, and in some animals no tumour remained at all. The morphology of the tumour remnants at day 22 was chaotic with a drastically changed histology, with presence of abundant cysts, low fractions of Ki67-positive cells, reduction in cell density, increased amounts of connective tissue and a decrease in necrotic regions. Again, apoptotic cells could be identified, scattered throughout the viable regions. Combining RT and RIT seems to generate an efficient treatment with convincing and long-lasting tumour growth inhibition, which is reflected in a highly aberrant histology within the tumour. Results obtained in this study indicate that both necrosis and apoptosis may be involved in the process leading to this efficient therapy of epithelially derived tumours.
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  • Giacobbo, B., et al. (author)
  • Metabolic changes in an animal model of Amyotrophic Lateral Sclerosis by [F-18]-Fluorodeoxyglucose
  • 2020
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 47:Suppl. 1, s. S638-S638
  • Journal article (other academic/artistic)abstract
    • Aim/Introduction: Amyotrophic Lateral Sclerosis (ALS) isa fatal neurodegenerative disorder that affects motorneurons, leading to muscle atrophy, paralysis, and eventuallyrespiratory failure. As with many other neurodegenerativedisorders, neuronal apoptosis is often associated with aloss of neuronal function and metabolic changes. [18F]-FDG is a well-validated biomarker to observe metabolicchanges in several brain disorders in humans, but its usein preclinical ALS research is not yet widespread. We aim tocompare [18F]-FDG uptake in SOD1G93A and wild-type beforethe development of terminal ALS symptoms.Materials and Methods: animals (6 SOD1WT, 7 SOD1G93A) were previouslygenotyped for mutant SOD1 using qPCR. When SOD1G93Aanimals started to develop ALS-like symptoms, animals werefasted for 4 hours and then injected intravenously with [18F]-FDG (injected dose of 10.8±2 MBq). One hour after injection,animals were placed in a microPET-CT scanner (MedisonanoPET-CT) and scanned (5 minutes for CT, 10 minutesfor PET). CT data was used for attenuation correction. Afterreconstruction, data were coregistered to an MRI templateand brain VOIs were created for several regions and dividedbetween left and right hemispheres using the Allen mousebrain atlas as a VOI template and the uptake of each ROIwas calculated to the whole-brain (SUVR) with T-test.P<0.05 was used for statistical significance.Results: OurSUVR data suggest a significant metabolic deregulationin SOD1G93A animals when analyzing [18F]-FDG in the brain.There was significant hypometabolism in anterior cingulatecortex (9% decrease in SOD1G93A vs. SOD1WT for both left and right hemispheres), in left entorhinal cortex (14%decrease), left hippocampus (12% decrease), right noseassociated primary somatosensory cortex (6% decrease),left supplementary somatosensory cortex (8% decrease),thalamus (11% and 8% for left and right, respectively),and right vermal region of the cerebellum (9% decrease).Hypermetabolism was, on the other hand, found in pallidum(12% increase in SOD1G93A vs. SOD1WT), lateral amygdala (41%and 64% increase in left and right, respectively), and corticalamygdala (98% increase for both left and right).Conclusion:These preliminary findings suggest a significant metabolicderegulation in animals with mutant SOD1 that developALS disease. Since animals were scanned after developingALS symptoms, further studies aimed to study brainmetabolism with [18F]-FDG in prodromal stages of diseaseare warranted. This would provide us better insight intothe usefulness of metabolic radiotracers for the detectionof disease onset and progression, as well as the efficacy oftherapeutic treatment strategies.References: None
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  • Giacobbo, B., et al. (author)
  • Social stress-dependent changes on behavior and inflammatory parameters in animals with HPA-axis disruption
  • 2020
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 47:Suppl.1, s. S639-S640
  • Journal article (other academic/artistic)abstract
    • Aim/Introduction: Chronic stress is associated with aderegulation of the hypothalamus-pituitary adrenal (HPA)axis and can result in behavioral abnormalities, such asdepressive behavior. Adrenalectomy (ADX) inhibits theproduction and release of corticosterone, impairingthe response towards stressors, and thus may preventstress-induced depressive behavior. We aim to determinebehavioral and neuroinflammatory effects of HPA-axisdisruption via bilateral adrenalectomy (ADX) in animalssubmitted to repeated social defeat (RSD).Materials and Methods: 8-weeks old male Wistar rats were dividedinto four groups: ADX+RSD; ADX+Control; Sham+RSD;Sham+Control. Seven days after ADX surgery, animals weresubmitted to a 5 days RSD or Control protocols. One- andtwo days after the last RSD trial, animals went through anopen field and social interaction test, respectively. 14 daysafter RSD, animals went through a 30 minutes [11C]-PBR28scan for microglia activation. Multifactorial ANOVA wasperformed for statistical assessment.Results: There was asignificant effect of RSD (p=0.038) and ADX (p=0.049) onthe social interaction of the animals, as well as an interactionbetween surgery and RSD (p=0.042). Post-hoc analysisshowed a significantly lower social interaction of Sham+RSDwhen compared with the other groups (vs. Control+ADX,p=0.032; Control+Sham, p=0.023; ADX+RSD, p=0.035).Open field analysis showed no anxiety-like behavior norlocomotion effect of RSD or ADX (p>0.05). Microglialactivation assessed through [11C]-PBR28 also showed noeffect of RSD or ADX (p>0.05).Conclusion: HPA-axis signalingdisruption is able to counterbalance the impairment on thesocial behavior of these animals. In contrast, no effects ofADX or RSD were observed in other behavioral paradigms.Neuroinflammation was also not observed two weeks afterthe RSD, suggesting that the inflammatory response ofmicroglial cells is too mild to be detected by PET or thatneuroinflammation was only transient and already resolvedat the time of measurement.References: None
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