UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Kinetic analysis of the translocator protein positron emission tomography ligand [F-18]GE-180 in the human brain

Feeney, C; Scott, G; Raffel, J; Roberts, S; Coello, C; Jolly, A; Searle, G; ... Sharp, DJ; + view all (2016) Kinetic analysis of the translocator protein positron emission tomography ligand [F-18]GE-180 in the human brain. European Journal of Nuclear Medicine and Molecular Imaging , 43 (12) pp. 2201-2210. 10.1007/s00259-016-3444-z. Green open access

[thumbnail of Published article]
Preview
Text (Published article)
Feeney_Kinetic analysis.pdf - Published Version

Download (1MB) | Preview
[thumbnail of Supplementary table]
Preview
Text (Supplementary table)
259_2016_3444_MOESM1_ESM.pdf

Download (53kB) | Preview
[thumbnail of Supplementary figure 1]
Preview
Image (Supplementary figure 1)
259_2016_3444_MOESM2_ESM.png

Download (97kB) | Preview
[thumbnail of Supplementary figure 2]
Preview
Image (Supplementary figure 2)
259_2016_3444_MOESM3_ESM.png

Download (239kB) | Preview

Abstract

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 [11C]PK-11195 limits accurate quantification. [18F]GE-180, a novel TSPO ligand, displays superior binding to [11C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [18F]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 [18F]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 [18F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.

Type: Article
Title: Kinetic analysis of the translocator protein positron emission tomography ligand [F-18]GE-180 in the human brain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00259-016-3444-z
Publisher version: https://doi.org/10.1007/s00259-016-3444-z
Language: English
Additional information: © The Author(s) 2016. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Positron emission tomography (PET), GE180, Translocator protein (TSPO), Kinetic analysis, Quantification, Neuroinflammation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10053894
Downloads since deposit
122Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item