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Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients
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- Forsberg, Anton (author)
- Karolinska Institutet
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- Juréus, Anders (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden
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- Cselényi, Zsolt (author)
- Karolinska Institutet
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- Eriksdotter, Maria (author)
- Karolinska Institutet
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- Freund-Levi, Yvonne, 1956- (author)
- Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; ; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden
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- Jeppsson, Fredrik (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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- Swahn, Britt-Marie (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden
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- Sandell, Johan (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden
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- Julin, Per (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden
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- Schou, Magnus (author)
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
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- Andersson, Jan (author)
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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- Johnström, Peter (author)
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
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- Varnäs, Katarina (author)
- Karolinska Institutet
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- Halldin, Christer (author)
- Karolinska Institutet
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- Farde, Lars (author)
- Karolinska Institutet
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- Svensson, Samuel (author)
- Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden
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(creator_code:org_t)
- 2013-01-17
- 2013
- English.
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer-Verlag New York. - 1619-7070 .- 1619-7089. ; 40:4, s. 580-593
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https://doi.org/10.1...
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Abstract
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- PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Alzheimer's disease
- Amyloid-beta imaging
- [C-11]AZD2995
- [C-11]AZD2184
- PET imaging
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Forsberg, Anton
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Juréus, Anders
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Cselényi, Zsolt
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Eriksdotter, Mar ...
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Freund-Levi, Yvo ...
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Jeppsson, Fredri ...
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Swahn, Britt-Mar ...
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Sandell, Johan
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Julin, Per
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Schou, Magnus
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Andersson, Jan
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Johnström, Peter
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Varnäs, Katarina
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Halldin, Christe ...
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Farde, Lars
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Svensson, Samuel
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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European Journal ...
- By the university
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Örebro University
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Karolinska Institutet