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  • 1. Carter, Stephen F.
    et al.
    Schöll, Michael
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Wall, Anders
    Engler, Henry
    Långström, Bengt
    Nordberg, Agneta
    Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by C-11-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining C-11-Pittsburgh Compound B and F-18-FDG2012In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, no 1, p. 37-46Article in journal (Refereed)
    Abstract [en]

    Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using C-11-deuterium-L-deprenyl (C-11-DED) to measure monoamine oxidase B located in astrocytes. Along with C-11-DED PET, C-11-Pittsburgh compound B (C-11-PIB; fibrillar A beta deposition), F-18-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: C-11-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the C-11-DED data. C-11-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional F-18-FDG uptake and C-11-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional C-11-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high C-11-PIB retention. Increased C-11-DED binding in most cortical and subcortical regions was observed in MCI C-11-PIB+ patients relative to controls, MCI C-11-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased C-11-DED binding throughout the brain of the MCI C-11-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

  • 2.
    Janek Strååt, Sara
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI). Stockholm University, Faculty of Science, Department of Physics.
    Jacobsson, Hans
    Andreassen, Björn
    Näslund, Ingemar
    Jonsson, Cathrine
    Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50 MV photon radiation therapyIn: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667Article in journal (Other academic)
  • 3. Rodriguez-Vieitez, Elena
    et al.
    Carter, Stephen F.
    Chiotis, Konstantinos
    Saint-Aubert, Laure
    Leuzy, Antoine
    Scholl, Michael
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Wall, Anders
    Langström, Bengt
    Nordberg, Agneta
    Comparison of Early-Phase C-11-Deuterium-L-Deprenyl and C-11-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease2016In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 7, p. 1071-1077Article in journal (Refereed)
    Abstract [en]

    The PET tracer C-11-deuterium-L-deprenyl (C-11-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase C-11-DED and C-11-Pittsburgh compound B (C-11-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which C-11-DED binding is influenced by brain perfusion was investigated. METHODS: C-11-DED, C-11-PiB, and F-18-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify C-11-DED binding. A simplified reference tissue model was applied to both C-11-DED and C-11-PiB to measure brain perfusion relative to the cerebellar gray matter (R-1) and binding potentials. C-11-PiB retention and F-18-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs). RESULTS: The strongest within-subject correlations with the corresponding R-1 values (R-1,R-DED and R-1,R-PiB, respectively) and with F-18-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R-1,R-DED/R-1,R-PiB and with F-18-FDG uptake, whereas C-11-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal F-18-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls. CONCLUSION: The 1- to 4-min early-frame intervals of C-11-DED or C-11-PiB are suitable surrogate measures for brain perfusion. C-11-DED binding is independent of brain perfusion, and thus C-11-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase C-11-DED and C-11-PiB perfusion appear to provide complementary rather than redundant information.

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