Imperial College London
Portrait Picture

ProfessorMagdalenaSastre

Faculty of Medicine, Department of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
//

Contact

 

+44 (0)20 7594 6673m.sastre

 
 
//

Location

 

406Burlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Rejc:2021:10.7150/thno.54589,
author = {Rejc, L and Gómez-Vallejo, V and Joya, A and Moreno, O and Egimendia, A and Castellnou, P and Ríos-Anglada, X and Cossío, U and Baz, Z and Passannante, R and Tobalina-Larrea, I and Ramos-Cabrer, P and Giralt, A and Sastre, M and Capetillo-Zarate, E and Koak, U and Knez, D and Gobec, S and Marder, M and Martin, A and Llop, J},
doi = {10.7150/thno.54589},
journal = {Theranostics},
pages = {6524--6559},
title = {Longitudinal evaluation of a novel BChE PET tracer as an early in vivo biomarker in the brain of a mouse model for Alzheimer disease},
url = {http://dx.doi.org/10.7150/thno.54589},
volume = {11},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Purpose: The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abundance. Here, we report 11C-labeling, in vivo stability, biodistribution, and longitudinal study on BChE abundance in the brains of control and 5xFAD (AD model) animals, using a potent BChE selective inhibitor, [11C]4, and positron emission tomography (PET) in combination with computerised tomography (CT). We correlate the results with in vivo amyloid beta (Aβ) deposition, longitudinally assessed by [18F]florbetaben-PET imaging.Methods: [11C]4 was radiolabelled through 11C-methylation. Metabolism studies were performed on blood and brain samples of female wild type (WT) mice. Biodistribution studies were performed in female WT mice using dynamic PET-CT imaging. Specific binding was demonstrated by ex vivo and in vivo PET imaging blocking studies in female WT and 5xFAD mice at the age of 7 months. Longitudinal PET imaging of BChE was conducted in female 5xFAD mice at 4, 6, 8, 10 and 12 months of age and compared to age-matched control animals. Additionally, Aβ plaque distribution was assessed in the same mice using [18F]florbetaben at the ages of 2, 5, 7 and 11 months. The results were validated by ex vivo staining of BChE at 4, 8, and 12 months and Aβ at 12 months on brain samples.Results: [11C]4 was produced in sufficient radiochemical yield and molar activity for the use in PET imaging. Metabolism and biodistribution studies confirmed sufficient stability in vivo, the ability of [11C]4 to cross the blood brain barrier (BBB) and rapid washout from the brain. Blocking studies confirmed specificity of the binding. Longitudinal PET studies showed increased levels of BChE in the cerebral cortex, hippocampus, stri
AU  - Rejc,L
AU  - Gómez-Vallejo,V
AU  - Joya,A
AU  - Moreno,O
AU  - Egimendia,A
AU  - Castellnou,P
AU  - Ríos-Anglada,X
AU  - Cossío,U
AU  - Baz,Z
AU  - Passannante,R
AU  - Tobalina-Larrea,I
AU  - Ramos-Cabrer,P
AU  - Giralt,A
AU  - Sastre,M
AU  - Capetillo-Zarate,E
AU  - Koak,U
AU  - Knez,D
AU  - Gobec,S
AU  - Marder,M
AU  - Martin,A
AU  - Llop,J
DO  - 10.7150/thno.54589
EP  - 6559
PY  - 2021///
SN  - 1838-7640
SP  - 6524
TI  - Longitudinal evaluation of a novel BChE PET tracer as an early in vivo biomarker in the brain of a mouse model for Alzheimer disease
T2  - Theranostics
UR  - http://dx.doi.org/10.7150/thno.54589
UR  - http://hdl.handle.net/10044/1/89022
VL  - 11
ER  -
Download