Imperial College London

DrRichardNicholas

Faculty of MedicineDepartment of Brain Sciences

Professor of Practice (Neurology)
 
 
 
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Contact

 

r.nicholas

 
 
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Location

 

12L12CLab BlockCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sridharan:2019:10.1007/s11307-019-01323-8,
author = {Sridharan, S and Raffel, J and Nandoskar, A and Record, C and Brooks, DJ and Owen, D and Sharp, D and Muraro, PA and Gunn, R and Nicholas, R},
doi = {10.1007/s11307-019-01323-8},
journal = {Molecular Imaging and Biology},
pages = {935--944},
title = {Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [18F]GE-180: a blocking study using XBD173 in multiple sclerosis normal appearing white and grey matter},
url = {http://dx.doi.org/10.1007/s11307-019-01323-8},
volume = {21},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Purpose: Positron emission tomography (PET) ligands exhibit different levels of non-displaceable binding in vivo. In the case of ligands for the 18 kDa translocator protein (TSPO), the component of non-displaceable binding for the most widely used radiotracer, [11C]-(R)-PK11195, is relatively high compared to that for newer TSPO ligands. Non-displaceable binding is not often quantified in humans in vivo, partially due to a lack of available ligands that are known to be safe with which to displace binding to the target receptor. Recently, however, a technique has been developed to quantify the non-displaceable binding of TSPO tracers in vivo, by blocking the receptor with the TSPO ligand XBD173 and comparing the total volume of distribution ( ) pre and post-blockade. Here, we used an occupancy plot to quantify the non-displaceable binding ( ) of the TSPO PET tracers [18F]GE-180 and [11C]PBR28 in cohorts of people with multiple sclerosis (MS). We also compared plots of subjects carrying both high and mixed binding affinity polymorphisms of TSPO to estimate while potentially avoiding the need for receptor blockade.Procedures: Twelve people with multiple sclerosis (MS) and high (HAB) or mixed (MAB) affinity binding for TSPO underwent baseline MRI and 90-minute dynamic [18F]GE-180 PET (n=6; 3 HAB and 3 MAB) or [11C]PBR28 PET (n=6; 3 HAB, 3 MAB). Either one week later ([18F]GE-180) or the same afternoon ([11C]PBR28), participants had repeat PET following a 90mg dose of XBD173. PET images were co-registered with T1 MR volumetric images and regions of interest (ROIs) were defined using the 83-region Hammers atlas. Arterial blood sampling was used to generate plasma input functions for the two-tissue compartment model to quantify . The non-displaceable fraction of the total volume of distribution ( ) was calculated using two independent methods: the occupancy plot (by modelling the differences in signal post XBD173), and the polymorphism plot (by modelling the differences in
AU - Sridharan,S
AU - Raffel,J
AU - Nandoskar,A
AU - Record,C
AU - Brooks,DJ
AU - Owen,D
AU - Sharp,D
AU - Muraro,PA
AU - Gunn,R
AU - Nicholas,R
DO - 10.1007/s11307-019-01323-8
EP - 944
PY - 2019///
SN - 1536-1632
SP - 935
TI - Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [18F]GE-180: a blocking study using XBD173 in multiple sclerosis normal appearing white and grey matter
T2 - Molecular Imaging and Biology
UR - http://dx.doi.org/10.1007/s11307-019-01323-8
UR - http://hdl.handle.net/10044/1/66971
VL - 21
ER -