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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
- Source :
- European Journal of Nuclear Medicine and Molecular Imaging
- Publisher :
- Springer Nature
-
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. Electronic supplementary material The online version of this article (doi:10.1007/s00259-012-2322-6) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
Pathology
Amyloid β
PET imaging
Aminopyridines
Disease
030218 nuclear medicine & medical imaging
Mice
Radioligand Assay
0302 clinical medicine
Carbon Radioisotopes
Aged, 80 and over
[11C]AZD2995
Benzoxazoles
High contrast
Aniline Compounds
medicine.diagnostic_test
Amyloid-β imaging
Brain
General Medicine
Middle Aged
Magnetic Resonance Imaging
Positron emission tomography
Radiology Nuclear Medicine and imaging
Female
Original Article
Alzheimer's disease
Alzheimer’s disease
Protein Binding
medicine.medical_specialty
Mice, Transgenic
Sensitivity and Specificity
03 medical and health sciences
Alzheimer Disease
medicine
Animals
Humans
Radiology, Nuclear Medicine and imaging
Benzothiazoles
Aged
Amyloid beta-Peptides
Binding Sites
business.industry
Case-control study
Magnetic resonance imaging
Pet imaging
medicine.disease
Thiazoles
Case-Control Studies
Positron-Emission Tomography
[11C]AZD2184
Radiopharmaceuticals
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 16197070
- Volume :
- 40
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- European Journal of Nuclear Medicine and Molecular Imaging
- Accession number :
- edsair.doi.dedup.....cb1c4f11c618305a7283ccb19023e2e0
- Full Text :
- https://doi.org/10.1007/s00259-012-2322-6