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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-04-2013 | Original Article

Low background and high contrast PET imaging of amyloid-β with [¹¹C]AZD2995 and [¹¹C]AZD2184 in Alzheimer’s disease patients

Authors: Anton Forsberg, Anders Juréus, Zsolt Cselényi, Maria Eriksdotter, Yvonne Freund-Levi, Fredrik Jeppsson, Britt-Marie Swahn, Johan Sandell, Per Julin, Magnus Schou, Jan Andersson, Peter Johnström, Katarina Varnäs, Christer Halldin, Lars Farde, Samuel Svensson

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2013

Abstract

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 [¹¹C]AZD2995 and [¹¹C]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. [³H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [¹¹C]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 [¹¹C]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 [¹¹C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [¹¹C]AZD2995. However, the very low nonspecific binding of [¹¹C]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.

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Title: Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer’s disease patients
Authors: Anton Forsberg
Anders Juréus
Zsolt Cselényi
Maria Eriksdotter
Yvonne Freund-Levi
Fredrik Jeppsson
Britt-Marie Swahn
Johan Sandell
Per Julin
Magnus Schou
Jan Andersson
Peter Johnström
Katarina Varnäs
Christer Halldin
Lars Farde
Samuel Svensson
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2013
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2322-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Low background and high contrast PET imaging of amyloid-β with [¹¹C]AZD2995 and [¹¹C]AZD2184 in Alzheimer’s disease patients

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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