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{Feeney:2016:10.1007/s00259-016-3444-z,
author = {Feeney, C and Scott, G and Raffel, J and Roberts, S and Coello, C and Jolly, A and Searle, G and Goldstone, AP and Brooks, DJ and Nicholas, RS and Trigg, W and Gunn, RN and Sharp, DJ},
doi = {10.1007/s00259-016-3444-z},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
pages = {2201--2210},
title = {Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain},
url = {http://dx.doi.org/10.1007/s00259-016-3444-z},
volume = {43},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - PURPOSE: PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [(11)C]PK-11195 limits accurate quantification. [(18)F]GE-180, a novel TSPO ligand, displays superior binding to [(11)C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [(18)F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. METHODS: Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [(18)F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. RESULTS: The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1) was 0.01 mL cm(-3) min(-1) indicating low extraction across the blood-brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm(-3) in the striatum to 0.38 mL cm(-3) in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. CONCLUSION: A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [(18)F]GE-180 in populations with neuroinflammatory disease is nee
AU - Feeney,C
AU - Scott,G
AU - Raffel,J
AU - Roberts,S
AU - Coello,C
AU - Jolly,A
AU - Searle,G
AU - Goldstone,AP
AU - Brooks,DJ
AU - Nicholas,RS
AU - Trigg,W
AU - Gunn,RN
AU - Sharp,DJ
DO - 10.1007/s00259-016-3444-z
EP - 2210
PY - 2016///
SN - 1619-7089
SP - 2201
TI - Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain
T2 - European Journal of Nuclear Medicine and Molecular Imaging
UR - http://dx.doi.org/10.1007/s00259-016-3444-z
UR - http://hdl.handle.net/10044/1/34488
VL - 43
ER -