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  • 1. Blomberg, Bjoern A.
    et al.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Saboury, Babak
    Alavi, Abass
    beta-Cell Mass Imaging with DTBZ Positron Emission Tomography: Is it Possible?2013In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 15, no 1, p. 1-2Article in journal (Refereed)
  • 2.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Direcks, Wieteke
    Emmering, Jasper
    van Tinteren, Harm
    Hoekstra, Otto S.
    van der Hoeven, Jacobus J.
    Molthoff, Carla F. M.
    Lammertsma, Adriaan A.
    Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer2012In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 14, no 6, p. 777-782Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Långström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Andrèn, Per E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lindhe, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svedberg, Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Hall, Håkan
    In vitro imaging techniques in neurodegenerative diseases2007In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 9, no 4, p. 161-175Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Olsen, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Aguilar, Ximena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fang, Xiaotian T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Erlandsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Syvänen, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer's Disease2018In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 20, no 4, p. 605-614Article in journal (Refereed)
    Abstract [en]

    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.

  • 5. Peeters, SarahG.J.A.
    et al.
    Dubois, Ludwig
    Lieuwes, NatasjaG.
    Laan, Dennis
    Mooijer, Martien
    Schuit, RobertC.
    Vullo, Daniela
    Supuran, ClaudiuT.
    Eriksson, Jonas
    VU University Medical Center Amsterdam.
    Windhorst, AlbertD.
    Lambin, Philippe
    [18F]VM4-037 MicroPET Imaging and Biodistribution of Two In Vivo CAIX-Expressing Tumor Models2015In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, p. 1-5Article in journal (Refereed)
  • 6. van Assema, Danielle M. E.
    et al.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Boellaard, Ronald
    Schuit, Robert C.
    Windhorst, Albert D.
    Scheltens, Philip
    Lammertsma, Adriaan A.
    van Berckel, Bart N. M.
    P-Glycoprotein Function at the Blood-Brain Barrier: Effects of Age and Gender2012In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 14, no 6, p. 771-776Article in journal (Refereed)
    Abstract [en]

    Purpose

    P-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.

    Procedures

    Thirty-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.

    Results

    Increased 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.

    Conclusions

    Decreased BBB Pgp is found with aging; however, effects of age on BBB Pgp function differ between men and women.

  • 7.
    Wållberg, Helena
    et al.
    Affibody AB, Stockholm, Sweden.
    Ahlgren, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Evaluation of the Radiocobalt-Labeled [MMA-DOTA-Cys61]-ZHER2:2395-Cys Affibody Molecule for Targeting of HER2-Expressing Tumors2010In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 12, no 1, p. 54-62Article in journal (Refereed)
    Abstract [en]

    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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