Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 40, Issue 4, pp 580-593

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Anton ForsbergAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet Email author 
  • , Anders JuréusAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & Development
  • , Zsolt CselényiAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska InstitutetAstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital
  • , Maria EriksdotterAffiliated withClinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDepartment of Geriatric Medicine, Karolinska University Hospital
  • , Yvonne Freund-LeviAffiliated withClinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDepartment of Geriatric Medicine, Karolinska University Hospital
  • , Fredrik JeppssonAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & DevelopmentScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet
  • , Britt-Marie SwahnAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & Development
  • , Johan SandellAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & Development
  • , Per JulinAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & Development
    • , Magnus SchouAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska InstitutetAstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital
    • , Jan AnderssonAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet
    • , Peter JohnströmAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska InstitutetAstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital
    • , Katarina VarnäsAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet
    • , Christer HalldinAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet
    • , Lars FardeAffiliated withCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska InstitutetAstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital
    • , Samuel SvenssonAffiliated withNeuroscience Research & Therapy Area, AstraZeneca Research & Development

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.

Keywords

Alzheimer’s disease Amyloid-β imaging [11C]AZD2995 [11C]AZD2184 PET imaging