| 1. |
- Byström, Johan, et al.
(författare)
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Reiterated homogenization of degenerate nonlinear elliptic equations
- 2002
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Ingår i: Chinese Annals of Mathematics. Series B. - 0252-9599 .- 1860-6261. ; 23:3, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- The authors study homogenization of some nonlinear partial differential equations of the form _ div (a (hx, h2 x, Duh)) = f , where a is periodic in the rst two arguments and monotone in the third. In particular the case where a satis es degenerated structure conditions is studied. It is proved that uh converges weakly in W0 1,1 (Ω) to the unique solution of a limit problem as h → ∞ . Moreover, explicit expressions for the limit problem are obtained.
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| 2. |
- Mohr, Barbara, et al.
(författare)
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Trifurcatia flabellata n. gen. n. sp., a putative monocotyledon angiosperm from the Lower Cretaceous Crato Formation (Brazil)
- 2002
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Ingår i: Fossil Record. - : Pensoft Publishers. - 1435-1943 .- 1860-1014. ; 5:1, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- The Lower Cretaceous Crato Formation (northeast Brazil) contains plant remains, here described as Trifurcatia flabellata n. gen. and n. sp., consisting of shoot fragments with jointed trifurcate axes, each axis bearing a single amplexicaul serrate leaf at the apex. The leaves show a flabellate acrodromous to parallelodromous venation pattern, with several primary, secondary and higher order cross-veins. This very unique fossil taxon shares many characters with monocots. However, this fossil taxon exhibits additional features which point to a partly reduced, and specialized plant, which probably enabled this plant to grow in (seasonally) dry, even salty environments. In der unterkretazischen Cratoformation (Nordostbrasilien) sind Pflanzenfossilien erhalten, die hier als Trifurcatia flabellata n. gen. n. sp. beschrieben werden. Sie bestehen aus trifurcaten Achsen, mit einem apikalen amplexicaulen fächerförmigen serraten Blatt. Diese Blätter zeigen eine flabellate bis acrodrome-paralellodrome Aderung mit Haupt- und Nebenadern und transversale Adern 3. Ordnung. Diese Merkmale sind typisch für Monocotyledone. Allerdings weist dieses Taxon einige Merkmale auf, die weder bei rezenten noch fossilen Monocotyledonen beobachtet werden. Sie müssen als besondere Anpassungen an einen (saisonal) trockenen und vielleicht übersalzenen Lebensraum dieser Pflanze interpretiert werden.
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| 3. |
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| 4. |
- Bailey, D. L., et al.
(författare)
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Combined PET/MRI : Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tubingen, Germany
- 2018
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Ingår i: Molecular Imaging and Biology. - : SPRINGER. - 1536-1632 .- 1860-2002. ; 20:1, s. 4-20
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Forskningsöversikt (refereegranskat)abstract
- The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.
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| 5. |
- Bailey, D. L., et al.
(författare)
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Combined PET/MRI : from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tubingen, Germany
- 2016
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 18:5, s. 637-650
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Tidskriftsartikel (refereegranskat)abstract
- This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tubingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.
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| 6. |
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| 7. |
- Delaney, Samantha, et al.
(författare)
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Site-Specific Photoaffinity Bioconjugation for the Creation of 89Zr-Labeled Radioimmunoconjugates
- 2023
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Ingår i: Molecular Imaging and Biology. - : Springer Nature. - 1536-1632 .- 1860-2002. ; 25:6, s. 1104-1114
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Site-specific approaches to bioconjugation produce well-defined and homogeneous immunoconjugates with potential for superior in vivo behavior compared to analogs synthesized using traditional, stochastic methods. The possibility of incorporating photoaffinity chemistry into a site-specific bioconjugation strategy is particularly enticing, as it could simplify and accelerate the preparation of homogeneous immunoconjugates for the clinic. In this investigation, we report the synthesis, in vitro characterization, and in vivo evaluation of a site-specifically modified, 89Zr-labeled radioimmunoconjugate created via the reaction between an mAb and an Fc-binding protein bearing a photoactivatable 4-benzoylphenylalanine residue. Procedures: A variant of the Fc-binding Z domain of protein A containing a photoactivatable, 4-benzoylphenylalanine residue — Z(35BPA) — was modified with desferrioxamine (DFO), combined with the A33 antigen-targeting mAb huA33, and irradiated with UV light. The resulting immunoconjugate — DFOZ(35BPA)-huA33 — was purified and characterized via SDS-PAGE, MALDI-ToF mass spectrometry, surface plasmon resonance, and flow cytometry. The radiolabeling of DFOZ(35BPA)-huA33 was optimized to produce [89Zr]Zr-DFOZ(35BPA)-huA33, and the immunoreactivity of the radioimmunoconjugate was determined with SW1222 human colorectal cancer cells. Finally, the in vivo performance of [89Zr]Zr-DFOZ(35BPA)-huA33 in mice bearing subcutaneous SW1222 xenografts was interrogated via PET imaging and biodistribution experiments and compared to that of a stochastically labeled control radioimmunoconjugate, [89Zr]Zr-DFO-huA33. Results: HuA33 was site-specifically modified with Z(35BPA)-DFO, producing an immunoconjugate with on average 1 DFO/mAb, high in vitro stability, and high affinity for its target. [89Zr]Zr-DFOZ(35BPA)-huA33 was synthesized in 95% radiochemical yield and exhibited a specific activity of 2 mCi/mg and an immunoreactive fraction of ~ 0.85. PET imaging and biodistribution experiments revealed that high concentrations of the radioimmunoconjugate accumulated in tumor tissue (i.e., ~ 40%ID/g at 120 h p.i.) but also that the Z(35BPA)-bearing immunoPET probe produced higher uptake in the liver, spleen, and kidneys than its stochastically modified cousin, [89Zr]Zr-DFO-huA33. Conclusions: Photoaffinity chemistry and an Fc-binding variant of the Z domain were successfully leveraged to create a novel site-specific strategy for the synthesis of radioimmunoconjugates. The probe synthesized using this method — DFOZ(35BPA)-huA33 — was well-defined and homogeneous, and the resulting radioimmunoconjugate ([89Zr]Zr-DFOZ(35BPA)-huA33) boasted high specific activity, stability, and immunoreactivity. While the site-specifically modified radioimmunoconjugate produced high activity concentrations in tumor tissue, it also yielded higher uptake in healthy organs than a stochastically modified analog, suggesting that optimization of this system is necessary prior to clinical translation.
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| 8. |
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| 9. |
- Eskola, Olli, et al.
(författare)
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Tracer Level Electrophilic Synthesis and Pharmacokinetics of the Hypoxia Tracer [F-18]EF5
- 2012
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 14:2, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [F-18]-fluorine ([F-18]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [F-18]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [F-18]EF5 to enable to study the pharmacokinetics at trace level. [F-18]EF5 was synthesized using high specific radioactivity electrophilic [F-18]F-2 as labelling reagent. Biodistribution of [F-18]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled metabolites was studied in mouse, rat and human plasma. On average, 595 +/- 153 MBq of [F-18]EF5 was produced. Specific radioactivity was 6.6 +/- 1.9 GBq/mu mol and the radiochemical purity exceeded 99.0%. [F-18]EF5 was distributed uniformly in tissues, with highest uptake in liver, kidney, and intestine. Several radiolabelled metabolites were detected in mouse plasma and tissues, whereas low amounts of metabolites were detected in human and rat plasma. [F-18]EF5 was synthesized by electrophilic labelling with high quality and high yields. Pharmacokinetics of [F-18]EF5 was determined at trace level in several species. Our results suggest that the trace-level approach does not affect the biodistribution of [F-18]EF5. Extensive metabolism was seen in mouse.
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| 10. |
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| 11. |
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| 12. |
- Lubberink, Mark, et al.
(författare)
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Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer
- 2012
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 14:6, s. 777-782
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Positron emission tomography using 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been suggested as a means for monitoring response to chemotherapy. The aim of this study was to evaluate the validity of simplified uptake measures for assessing response to chemotherapy using [18F]FLT in locally advanced breast cancer (LABC).Procedures:Fifteen LABC patients underwent dynamic [18F]FLT scans both prior to and after the first cycle of chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide. The net uptake rate constant of [18F]FLT, K i , determined by non-linear regression (NLR) of an irreversible two-tissue compartment model was used as the gold standard. In addition to Patlak graphical analysis, standardised uptake values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing [18F]FLT data. Correlations and relationships between simplified uptake measures and NLR before and after chemotherapy were assessed using regression analysis.Results: No significant differences in both pre- and post-chemotherapy relationships between any of the simplified uptake measures and NLR were found. However, changes in SUV between baseline and post-therapy scans showed a significant negative bias and slope less than one, while TBR did not.Conclusions:In LABC, TBR instead of SUV may be preferred for monitoring response to chemotherapy with [18F]FLT.
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| 13. |
- Långström, Bengt, et al.
(författare)
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In vitro imaging techniques in neurodegenerative diseases
- 2007
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 9:4, s. 161-175
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegeneration induces various changes in the brain, changes that may be investigated using neuroimaging techniques. The in vivo techniques are useful for the visualization of major changes, and the progressing abnormalities may also be followed longitudinally. However, to study and quantify minor abnormalities, neuroimaging of postmortem brain tissue is used. These in vitro methods are complementary to the in vivo techniques and contribute to the knowledge of pathophysiology and etiology of the neurodegenerative diseases. In vitro radioligand autoradiography has given great insight in the involvement of different neuronal receptor systems in these diseases. Data on the dopamine and cholinergic systems in neurodegeneration are discussed in this review. Also, the amyloid plaques are studied using in vitro radioligand autoradiography. Using one of the newer methods, imaging matrix-assisted laser desorption ionization mass spectrometry, the distribution of a large number of peptides and proteins may be detected in vitro on brain cryosections. In this overview, we describe in vitro imaging techniques in the neurodegenerative diseases as a complement to in vivo positron emission tomography and single photon emission computed tomography imaging.
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| 14. |
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| 15. |
- Meier, Silvio R., et al.
(författare)
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Pinpointing Brain TREM2 Levels in Two Mouse Models of Alzheimer's Disease
- 2021
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Ingår i: Molecular Imaging and Biology. - : Springer. - 1536-1632 .- 1860-2002. ; 23, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by brain microglia. Microglial activation, as observed in Alzheimer's disease (AD) as well as in transgenic mice expressing human amyloid-beta, appears to increase soluble TREM2 (sTREM2) levels in CSF and brain. In this study, we used two different transgenic mouse models of AD pathology and investigated the potential of TREM2 to serve as an in vivo biomarker for microglial activation in AD.PROCEDURES: We designed and generated a bispecific antibody based on the TREM2-specific monoclonal antibody mAb1729, fused to a single-chain variable fragment of the transferrin receptor binding antibody 8D3. The 8D3-moiety enabled transcytosis of the whole bispecific antibody across the blood-brain barrier. The bispecific antibody was radiolabeled with I-125 (ex vivo) or I-124 (PET) and administered to transgenic AD and wild-type (WT) control mice. Radioligand retention in the brain of transgenic animals was compared to WT mice by isolation of brain tissue at 24 h or 72 h, or with in vivo PET at 24 h, 48 h, and 72 h. Intrabrain distribution of radiolabeled mAb1729-scFv8D3CL was further studied by autoradiography, while ELISA was used to determine TREM2 brain concentrations.RESULTS: Transgenic animals displayed higher total exposure, calculated as the AUC based on SUV determined at 24h, 48h, and 72h post injection, of PET radioligand [124I]mAb1729-scFv8D3CL than WT mice. However, differences were not evident in single time point PET images or SUVs. Ex vivo autoradiography confirmed higher radioligand concentrations in cortex and thalamus in transgenic mice compared to WT, and TREM2 levels in brain homogenates were considerably higher in transgenic mice compared to WT.CONCLUSION: Antibody-based radioligands, engineered to enter the brain, may serve as PET radioligands to follow changes of TREM2 in vivo, but antibody formats with faster systemic clearance to increase the specific signal in relation to that from blood in combination with antibodies showing higher affinity for TREM2 must be developed to further progress this technique for in vivo use.
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| 16. |
- Olsen, Malin, et al.
(författare)
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Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer's Disease
- 2018
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Ingår i: Molecular Imaging and Biology. - : SPRINGER. - 1536-1632 .- 1860-2002. ; 20:4, s. 605-614
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (A beta) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-l-[C-11]deprenyl ([C-11]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i.e., two well-established markers of astrogliosis, during A beta pathology progression. APP(ArcSwe) mice (n = 37) and wild-type (WT) control mice (n = 23), 2-16-month old, were used to investigate biomarkers of astrogliosis. The radioligand, [C-11]DED, was used as an in vivo marker while GFAP, vimentin, and MAO-B were used to investigate astrogliosis and macrophage-associated lectin (Mac-2) to investigate microglia/macrophage activation by immunohistochemistry of the mouse brain. A beta and GFAP levels were also measured with ELISA in brain homogenates. The intrabrain levels of aggregated A beta and reactive astrocytes were found to be elevated in APP(ArcSwe) compared with WT mice. GFAP and vimentin expression increased with age, i.e., with A beta pathology, in the APP(ArcSwe) mice. This was not the case for in vivo marker [C-11]DED that showed elevated binding of the same magnitude in APP(ArcSwe) mice compared with WT mice at both 8 and 16 months. Further, immunohistochemistry indicated that there was limited co-expression of MAO-B and GFAP. MAO-B levels are increased early in A beta pathology progression, while GFAP and vimentin appear to increase later, most likely as a consequence of abundant A beta plaque formation. Thus, [C-11]DED is a useful PET radioligand for the detection of changes in MAO-B at an early stage of AD progression but does not measure the total extent of astrogliosis at advanced stages of A beta pathology.
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| 17. |
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| 18. |
- Rubins, Daniel J., et al.
(författare)
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In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1
- 2021
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Ingår i: Molecular Imaging and Biology. - : Springer. - 1536-1632 .- 1860-2002. ; 23, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In vivo imaging of programmed death ligand 1 (PD-L1) during immunotherapy could potentially monitor changing PD-L1 expression and PD-L1 expression heterogeneity within and across tumors. Some protein constructs can be used for same-day positron emission tomography (PET) imaging. Previously, we evaluated the PD-L1-targeting Affibody molecule [F-18]AlF-NOTA-Z(PD-L1_1) as a PET tracer in a mouse tumor model of human PD-L1 expression. In this study, we evaluated the affinity-matured Affibody molecule Z(PD-L1_4), to determine if improved affinity for PD-L1 resulted in increased in vivo targeting of PD-L1.Procedures: Z(PD-L1_4) was conjugated with NOTA and radiolabeled with either [F-18]AlF or Ga-68. [F-18]AlF-NOTA-Z(PD-L1_4) and [Ga-68]NOTA-Z(PD-L1_4) were evaluated in immunocompromised mice with LOX (PD-L1+) and SUDHL6 (PD-L1-) tumors with PET and ex vivo biodistribution measurements. In addition, whole-body PET studies were performed in rhesus monkeys to predict human biodistribution in a model with tracer binding to endogenous PD-L1, and to calculate absorbed radiation doses.Results: Ex vivo biodistribution measurements showed that both tracers had > 25 fold higher accumulation in LOX tumors than SUDHL6 ([F-18]AlF-NOTA-Z(PD-L1_4): LOX: 8.7 +/- 0.7 %ID/g (N = 4) SUDHL6: 0.2 +/- 0.01 %ID/g (N = 6), [Ga-68]NOTA-Z(PD-L1_4): LOX: 15.8 +/- 1.0 %ID/g (N = 6) SUDHL6: 0.6 +/- 0.1 %ID/g (N = 6)), considerably higher than Z(PD-L1_1). In rhesus monkeys, both PET tracers showed fast clearance through kidneys and low background signal in the liver ([F-18]AlF-NOTA-Z(PD-L1_4): 1.26 +/- 0.13 SUV, [Ga-68]NOTA-Z(PD-L1_4): 1.11 +/- 0.06 SUV). PD-L1-expressing lymph nodes were visible in PET images, indicating in vivo PD-L1 targeting. Dosimetry estimates suggest that both PET tracers can be used for repeated clinical studies, although high kidney accumulation may limit allowable radioactive doses.Conclusions: [F-18]AlF-NOTA-Z(PD-L1_4) and [Ga-68]NOTA-Z(PD-L1_4) are promising candidates for same-day clinical PD-L1 PET imaging, warranting clinical evaluation. The ability to use either [F-18] or [Ga-68] may expand access to clinical sites.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Siegel, T. P., et al.
(författare)
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Mass Spectrometry Imaging and Integration with Other Imaging Modalities for Greater Molecular Understanding of Biological Tissues
- 2018
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 20:6, s. 888-901
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Forskningsöversikt (refereegranskat)abstract
- Over the last two decades, mass spectrometry imaging (MSI) has been increasingly employed to investigate the spatial distribution of a wide variety of molecules in complex biological samples. MSI has demonstrated its potential in numerous applications from drug discovery, disease state evaluation through proteomic and/or metabolomic studies. Significant technological and methodological advancements have addressed natural limitations of the techniques, i.e., increased spatial resolution, increased detection sensitivity especially for large molecules, higher throughput analysis and data management. One of the next major evolutions of MSI is linked to the introduction of imaging mass cytometry (IMC). IMC is a multiplexed method for tissue phenotyping, imaging signalling pathway or cell marker assessment, at sub-cellular resolution (1m). It uses MSI to simultaneously detect and quantify up to 30 different antibodies within a tissue section. The combination of MSI with other molecular imaging techniques can also provide highly relevant complementary information to explore new scientific fields. Traditionally, classical histology (especially haematoxylin and eosin-stained sections) is overlaid with molecular profiles obtained by MSI. Thus, MSI-based molecular histology provides a snapshot of a tissue microenvironment and enables the correlation of drugs, metabolites, lipids, peptides or proteins with histological/pathological features or tissue substructures. Recently, many examples combining MSI with other imaging modalities such as fluorescence, confocal Raman spectroscopy and MRI have emerged. For instance, brain pathophysiology has been studied using both MRI and MSI, establishing correlations between in and ex vivo molecular imaging techniques. Endogenous metabolite and small peptide modulation were evaluated depending on disease state. Here, we review advanced hot topics' in MSI development and explore the combination of MSI with established molecular imaging techniques to improve our understanding of biological and pathophysiological processes.
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| 23. |
- Strome, Elissa, et al.
(författare)
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Animal models of neurodegenerative disease: Insights from in vivo imaging studies
- 2007
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 9:4, s. 186-195
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Forskningsöversikt (refereegranskat)abstract
- Animal models have been used extensively to understand the etiology and pathophysiology of human neurodegenerative diseases, and are an essential component in the development of therapeutic interventions for these disorders. In recent years, technical advances in imaging modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have allowed the use of these techniques for the evaluation of functional, neurochemical, and anatomical changes in the brains of animals. Combining animal models of neurodegenerative disorders with neuroimaging provides a powerful tool to follow the disease process, to examine compensatory mechanisms, and to investigate the effects of potential treatments preclinically to derive knowledge that will ultimately inform our clinical decisions. This article reviews the literature on the use of PET and MRI in animal models of Parkinson's disease, Huntington's disease, and Alzheimer's disease, and evaluates the strengths and limitations of brain imaging in animal models of neurodegenerative diseases.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Tuncel, Hayel, et al.
(författare)
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Effect of Shortening the Scan Duration on Quantitative Accuracy of [18F]Flortaucipir Studies
- 2021
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 23:4, s. 604-613
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dynamic positron emission tomography (PET) protocols allow for accurate quantification of [18F]flortaucipir-specific binding. However, dynamic acquisitions can be challenging given the long required scan duration of 130 min. The current study assessed the effect of shorter scan protocols for [18F]flortaucipir on its quantitative accuracy. Procedures: Two study cohorts with Alzheimer’s disease (AD) patients and healthy controls (HC) were included. All subjects underwent a 130-min dynamic [18F]flortaucipir PET scan consisting of two parts (0–60/80–130 min) post-injection. Arterial sampling was acquired during scanning of the first cohort only. For the second cohort, a second PET scan was acquired within 1–4 weeks of the first PET scan to assess test-retest repeatability (TRT). Three alternative time intervals were explored for the second part of the scan: 80–120, 80–110 and 80–100 min. Furthermore, the first part of the scan was also varied: 0–50, 0–40 and 0–30 min time intervals were assessed. The gap in the reference TACs was interpolated using four different interpolation methods: population-based input function 2T4k_VB (POP-IP_2T4k_VB), cubic, linear and exponential. Regional binding potential (BPND) and relative tracer delivery (R1) values estimated using simplified reference tissue model (SRTM) and/or receptor parametric mapping (RPM). The different scan protocols were compared to the respective values estimated using the original scan acquisition. In addition, TRT of the RPM BPND and R1 values estimated using the optimal shortest scan duration was also assessed. Results: RPM BPND and R1 obtained using 0–30/80–100 min scan and POP-IP_2T4k_VB reference region interpolation had an excellent correlation with the respective parametric values estimated using the original scan duration (r2 > 0.95). The TRT of RPM BPND and R1 using the shortest scan duration was − 1 ± 5 % and − 1 ± 6 % respectively. Conclusions: This study demonstrated that [18F]flortaucipir PET scan can be acquired with sufficient quantitative accuracy using only 50 min of dual-time-window scanning time.
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| 28. |
- van Assema, Danielle M. E., et al.
(författare)
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P-Glycoprotein Function at the Blood-Brain Barrier : Effects of Age and Gender
- 2012
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 14:6, s. 771-776
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Tidskriftsartikel (refereegranskat)abstract
- PurposeP-glycoprotein (Pgp) is an efflux transporter involved in transport of several compounds across the blood–brain barrier (BBB). Loss of Pgp function with increasing age may be involved in the development of age-related disorders, but this may differ between males and females. Pgp function can be quantified in vivo using (R)-[11C]verapamil and positron emission tomography. The purpose of this study was to assess global and regional effects of both age and gender on BBB Pgp function.ProceduresThirty-five healthy men and women in three different age groups were included. Sixty minutes dynamic (R)-[11C]verapamil scans with metabolite-corrected arterial plasma input curves were acquired. Grey matter time–activity curves were fitted to a validated constrained two-tissue compartment plasma input model, providing the volume of distribution (V T) of (R)-[11C]verapamil as outcome measure.ResultsIncreased V T of (R)-[11C]verapamil with aging was found in several large brain regions in men. Young and elderly women showed comparable V T values. Young women had higher V T compared with young men.ConclusionsDecreased BBB Pgp is found with aging; however, effects of age on BBB Pgp function differ between men and women.
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| 29. |
- Wallberg, Helena, et al.
(författare)
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Evaluation of the Radiocobalt-Labeled [MMA-DOTA-Cys(61)]-Z(HER2:2395)-Cys Affibody Molecule for Targeting of HER2-Expressing Tumors
- 2010
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 12:1, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Imaging using positron emission tomography (PET) in the field of nuclear medicine is becoming increasingly important. The aim of this study was to develop a method for labeling of affibody molecules with radiocobalt for PET applications. The human epidermal growth factor receptors type 2 (HER2) binding affibody molecule DOTA-Z(2395)-C was radiolabeled with (57)Co (used as a surrogate of (55)Co). The binding specificity and cellular processing of the labeled compound was studied in vitro followed by in vivo characterization in normal and tumor-bearing mice. Furthermore, a comparative biodistribution study was performed with a (111)In-labeled counterpart. DOTA-Z(2395)-C was successfully labeled with radiocobalt with nearly quantitative yield. The compound displayed good retention on cells over time and high tumor accumulation of radioactivity in animal studies. Imaging studies showed clear visualization of HER2-positive tumors. Furthermore, the radiocobalt label provided better tumor-to-organ ratios than (111)In. Radiocobalt is a promising label for affibody molecules for future PET applications.
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| 31. |
- Wållberg, Helena, et al.
(författare)
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Evaluation of the Radiocobalt-Labeled [MMA-DOTA-Cys61]-ZHER2:2395-Cys Affibody Molecule for Targeting of HER2-Expressing Tumors
- 2010
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 12:1, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Imaging using positron emission tomography (PET) in the field of nuclear medicine is becoming increasingly important. The aim of this study was to develop a method for labeling of affibody molecules with radiocobalt for PET applications. PROCEDURES: The human epidermal growth factor receptors type 2 (HER2) binding affibody molecule DOTA-Z(2395)-C was radiolabeled with (57)Co (used as a surrogate of (55)Co). The binding specificity and cellular processing of the labeled compound was studied in vitro followed by in vivo characterization in normal and tumor-bearing mice. Furthermore, a comparative biodistribution study was performed with a (111)In-labeled counterpart. RESULTS: DOTA-Z(2395)-C was successfully labeled with radiocobalt with nearly quantitative yield. The compound displayed good retention on cells over time and high tumor accumulation of radioactivity in animal studies. Imaging studies showed clear visualization of HER2-positive tumors. Furthermore, the radiocobalt label provided better tumor-to-organ ratios than (111)In. CONCLUSIONS: Radiocobalt is a promising label for affibody molecules for future PET applications.
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- Krajnovic, Sinisa, 1970, et al.
(författare)
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Exploring the Flow Around a Simplified Bus with Large Eddy Simulation and Topological Tools
- 2004
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Ingår i: Lecture Notes in Applied and Computational Mechanics. - 1860-0816 .- 1613-7736. ; , s. 49-64
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Konferensbidrag (refereegranskat)abstract
- The results of the large eddy simulation of the flow around a simplified bus presented in Krajnovic and Davidson (Journal of Fluids Engineering,125, pages 500-509, 2002) are used to describe this flow in detail. Using time-averaged trace lines on the surface of the body, the patterns of the shear-stress lines are revealed and used to identify bifurcation lines and critical points (zero-shear-stress points) in the flow. This information is then used to establish a complete picture of the flow on the surface of the body that can be used for understanding soiling and accumulation of water on the surface or in determinations of aeroacoustic noise sources. Kinematical investigations of the flow in two symmetry planes were done to reveal the critical points in the flow. With this it was proven that the flow resulting from numerical simulation is kinematically possible.
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