Kinetic analysis of the translocator protein positron emission tomography ligand 18FGE-180 in the human brainReport as inadecuate




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European Journal of Nuclear Medicine and Molecular Imaging

, Volume 43, Issue 12, pp 2201–2210

First Online: 28 June 2016Received: 28 January 2016Accepted: 14 June 2016DOI: 10.1007-s00259-016-3444-z

Cite this article as: Feeney, C., Scott, G., Raffel, J. et al. Eur J Nucl Med Mol Imaging 2016 43: 2201. doi:10.1007-s00259-016-3444-z

Abstract

PurposePET 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 CPK-11195 limits accurate quantification. FGE-180, a novel TSPO ligand, displays superior binding to CPK-11195 in vitro. Our objectives were to: 1 evaluate tracer characteristics of FGE-180 in the brains of healthy human subjects; and 2 investigate whether the TSPO Ala147Thr polymorphism influences outcome measures.

MethodsTen volunteers five high-affinity binders, HABs, and five mixed-affinity binders, MABs underwent a dynamic PET scan with arterial sampling after injection of FGE-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 VT 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.

ResultsThe two-tissue compartment model was the best model. The average regional delivery rate constant K1 was 0.01 mL cm min indicating low extraction across the blood–brain barrier 1 %. The estimated median VT across all ROIs was also low, ranging from 0.16 mL cm in the striatum to 0.38 mL cm in the thalamus. There were no significant differences in VT between HABs and MABs across all ROIs.

ConclusionA reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction approximately 1 % and low VT estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of FGE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.

KeywordsPositron emission tomography PET GE180 Translocator protein TSPO Kinetic analysis Quantification Neuroinflammation Electronic supplementary materialThe online version of this article doi:10.1007-s00259-016-3444-z contains supplementary material, which is available to authorized users.

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Author: Claire Feeney - Gregory Scott - Joel Raffel - S. Roberts - Christopher Coello - Amy Jolly - Graham Searle - A. P. Goldsto

Source: https://link.springer.com/







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