18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke

Boutin, Hervé; Murray, Kristen; Pradillo, Jesús M.; Maroy, Renaud; Smigova, Alison; Gerhard, Alexander; Jones, Paul A.; Trigg, William

doi:10.1007/s00259-014-2939-8

Cited by 113 publications

(162 citation statements)

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“…Consistent with a preclinical study (8), high-performance liquid chromatography revealed 3 separate 18 F-GE180 plasma metabolites, with a similar profile in HAB and MAB and no significant differences between HABs and MABs in plasma-to-blood ratios. The plasma-to-blood ratio for tracers crossing the BBB by passive diffusion is close to unity at the beginning of PET.…”

Section: Discussionsupporting

confidence: 84%

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Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

et al. 2016

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Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed thirdgeneration TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Methods: Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18 F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. Results: 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (V T ) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with V T in the kinetic model, which could be used for voxelwise analysis. Conclusion: We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18 F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low V T , the methodology presented here forms the basis for quantification for future PET studies using 18 F-GE180 in different pathologies.

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Section: Discussionsupporting

confidence: 84%

“…Flutriciclamide ( 18 F-GE180) has been identified as a promising TSPO tracer in preclinical models of stroke and lipopolysaccharideinduced central nervous system inflammation (8,9). Here we report the results of a study evaluating 18 F-GE180 PET in healthy human brains.…”

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confidence: 96%

Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

et al. 2016

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“…Although 8 F-GE-180 imaging has resulted in improved signal-to-noise ratio and lower nonspecific binding in animal models of cerebral infarction, it has yet been applied to image inflammation associated with IHD. 37 The use of both 11 C-PK11195 and 18 F-GE-180 for imaging inflammation, however, may be limited by the presence of genetic polymorphisms that affect the binding capacity of these agents in some individuals 38 as well as high myocardial uptake making coronary plaque imaging challenging.…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging of Inflammation in Ischemic Heart Disease

Bakerman

Wardak

Nguyen

2018

Curr Cardiovasc Imaging Rep

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Purpose of Review Ischemic heart disease is caused by atherosclerosis, the build-up of plaque in the coronary arteries, which can lead to the development of heart attacks and heart muscle damage. Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. Recent studies have suggested that the immune system may play a greater role in the development of plaque rupture and adverse left ventricular remodeling after myocardial infarction. Understanding the molecular processes by which inflammation contributes to the pathophysiology of ischemic heart disease is, therefore, worthwhile. This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease. Recent Findings A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, including radioisotopes and nanoparticles, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging. Summary While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed. Nevertheless, imaging inflammation using PET or MRI has the potential to become an important adjunct tool to improve the diagnosis, risk stratification, and therapeutic monitoring of patients with ischemic heart disease.

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“…After genotyping, no difference in 18 F-GE-180 uptake was found between mediumaffinity and high-affinity binders, nor in tumours and normal brain, indicating a relatively low sensitivity of 18 F-GE-180 to the rs6971 polymorphism. The image quality obtained with TSPO PET using 18 F-GE-180 appears to be definitively superior to that obtained with previous TSPO ligands [10,15]. The conclusions that can be drawn from these data with respect to the identification of tumour extent, however, are limited since no data on regional histology were provided.…”

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confidence: 73%

“…In several preclinical studies in which TSPO tracers were directly compared with each other, 18 F-GE-180 has been proven to be superior to other TSPO ligands. In an ischemia model of the rat, 18 F-GE-180 showed a higher signal-to-noise ratio and lower nonspecific binding than 11 C-PK11195 [10]. Also, in a mouse model of mild neuroinflammation obtained by injecting low doses of endotoxin into the brain, only 18 F-GE-180, and not the second generation tracer 18 F-DPA-714 demonstrated a significantly higher binding potential and signal-to-noise ratio than 11 C-PK11195 [11].…”

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confidence: 91%

TSPO PET using 18F-GE-180: a new perspective in neurooncology?

Langen

Willuweit

2017

Eur J Nucl Med Mol Imaging

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18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke

Cited by 113 publications

References 39 publications

Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Molecular Imaging of Inflammation in Ischemic Heart Disease

TSPO PET using 18F-GE-180: a new perspective in neurooncology?

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18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke

Cited by 113 publications

References 39 publications

Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Molecular Imaging of Inflammation in Ischemic Heart Disease

TSPO PET using 18F-GE-180: a new perspective in neurooncology?

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Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Flutriciclamide (¹⁸F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein