Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Brain Sciences

Edmond and Lily Safra Chair. Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Owen:2011:10.2967/jnumed.110.079459,
author = {Owen, DR and Gunn, RN and Rabiner, EA and Bennacef, I and Fujita, M and Kreisl, WC and Innis, RB and Pike, VW and Reynolds, R and Matthews, PM and Parker, CA},
doi = {10.2967/jnumed.110.079459},
journal = {J Nucl Med},
pages = {24--32},
title = {Mixed-affinity binding in humans with 18-kDa translocator protein ligands},
url = {http://dx.doi.org/10.2967/jnumed.110.079459},
volume = {52},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 11C-PBR28 PET can detect the 18-kDa translocator protein (TSPO) expressed within macrophages. However, quantitative evaluation of the signal in brain tissue from donors with multiple sclerosis (MS) shows that PBR28 binds the TSPO with high affinity (binding affinity [Ki], approximately 4 nM), low affinity (Ki, approximately 200 nM), or mixed affinity (2 sites with Ki, approximately 4 nM and approximately 300 nM). Our study tested whether similar binding behavior could be detected in brain tissue from donors with no history of neurologic disease, with TSPO-binding PET ligands other than 11C-PBR28, for TSPO present in peripheral blood, and with human brain PET data acquired in vivo with 11C-PBR28. METHODS: The affinity of TSPO ligands was measured in the human brain postmortem from donors with a history of MS (n=13), donors without any history of neurologic disease (n=20), and in platelets from healthy volunteers (n=13). Binding potential estimates from thirty-five 11C-PBR28 PET scans from an independent sample of healthy volunteers were analyzed using a gaussian mixture model. RESULTS: Three binding affinity patterns were found in brains from subjects without neurologic disease in similar proportions to those reported previously from studies of MS brains. TSPO ligands showed substantial differences in affinity between subjects classified as high-affinity binders (HABs) and low-affinity binders (LABs). Differences in affinity between HABs and LABs are approximately 50-fold with PBR28, approximately 17-fold with PBR06, and approximately 4-fold with DAA1106, DPA713, and PBR111. Where differences in affinity between HABs and LABs were low ( approximately 4-fold), distinct affinities were not resolvable in binding curves for mixed-affinity binders (MABs), which appeared to express 1 class of sites with an affinity approximately equal to the mean of those for HABs and LABs. Mixed-affinity binding was detected in platelets from an independent sample (HAB, 69%; MAB, 31%), al
AU - Owen,DR
AU - Gunn,RN
AU - Rabiner,EA
AU - Bennacef,I
AU - Fujita,M
AU - Kreisl,WC
AU - Innis,RB
AU - Pike,VW
AU - Reynolds,R
AU - Matthews,PM
AU - Parker,CA
DO - 10.2967/jnumed.110.079459
EP - 32
PY - 2011///
SN - 1535-5667
SP - 24
TI - Mixed-affinity binding in humans with 18-kDa translocator protein ligands
T2 - J Nucl Med
UR - http://dx.doi.org/10.2967/jnumed.110.079459
UR - http://www.ncbi.nlm.nih.gov/pubmed/21149489
UR - http://hdl.handle.net/10044/1/19989
VL - 52
ER -