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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 43; no. 12; pp. 2201 - 2210
• Main Authors: Feeney, Claire, Scott, Gregory, Raffel, Joel, Roberts, S., Coello, Christopher, Jolly, Amy, Searle, Graham, Goldstone, A. P., Brooks, David J., Nicholas, Richard S., Trigg, William, Gunn, Roger N., Sharp, David J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2016; Springer Nature B.V
• Subjects: Adult; Algorithms; Brain; Brain - diagnostic imaging; Brain - metabolism; Carbazoles - pharmacokinetics; Cardiology; Computer Simulation; Humans; Image Enhancement - methods; Image Interpretation, Computer-Assisted - methods; Imaging; Kinetics; Ligands; Medicine; Medicine & Public Health; Metabolic Clearance Rate; Middle Aged; Models, Neurological; Molecular Imaging - methods; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Position tracking; Positron-Emission Tomography - methods; Proteins; Radiology; Radiopharmaceuticals - pharmacokinetics; Receptors, GABA - genetics; Receptors, GABA - metabolism; Reproducibility of Results; Sensitivity and Specificity; Tomography; Neuroinflammation; Positron emission tomography (PET); Kinetic analysis; GE180; Quantification; Translocator protein (TSPO)
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-016-3444-z

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 needed to determine its suitability for quantitative assessment of TSPO expression.