[18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18kDa (TSPO)

Wadsworth, Harry J.; Jones, Paul A.; Chau, Wai-Fung; Durrant, Clare; Fouladi, Naghmeh; Passmore, Joanna; O'shea, D. M.; Wynn, Duncan; Morisson-Iveson, Véronique; Ewan, Amanda L.; Thaning, Mikkel; Mantzilas, Dimitrios; Gausemel, Ingvil; Khan, Imtiaz Ahmed; Black, Andrew; Avory, Michelle; Trigg, William

doi:10.1016/j.bmcl.2011.12.084

Cited by 120 publications

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“…Despite the fact that species differences have been observed in the BBB structure (19) and other novel brain PET tracers (20), the significant difference observed between human and preclinical models in 18 F-GE180 could be primarily due to a significantly higher binding to plasma protein in humans. 18 F-GE180 preclinical studies demonstrated that, in rats, there is a clear regional differentiation of high-TSPOexpressing regions (olfactory bulbs) compared with low-TSPO-expressing regions (striatum) (21). In this study, 5 subjects (1 MAB and 4 HABs) revealed lowest uptake in the striatum: 3 (MABs) showed lowest uptake in the cerebellum and 2 (HABs) showed a more generalized distribution of TSPO expression.…”

Section: Discussionmentioning

confidence: 47%

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: Discussionmentioning

confidence: 47%

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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“…This fact has previously been used to validate TSPO tracers in healthy animals (10). Previously, it has been reported that the TSPO protein is also expressed in the ependymal cells (34) and cells within the choroid plexus (9,35).…”

Section: Discussionmentioning

confidence: 91%

“…11 C-(R)-PK11195 and 18 F-GE-180 were synthesized according to methods first described by Hashimoto (15), Shah et al (16), and Wadsworth et al (10), with some modifications (the supplemental methods provide details; supplemental materials are available at http://jnm.snmjournals. org).…”

Section: Tracer Productionmentioning

confidence: 99%

“…18 F-GE-180 (S-N,N-diethyl-9-[2-18 F-fluoroethyl]-5-methoxy 2,3,4,9-tetrahydro-1H-carbazole-4-carboxamide, Fig. 1) is the lead compound from a new series of tricyclic indoles, which have been shown to have a high affinity for TSPO (10). According to a preliminary in vitro and biodistribution study, 18 F-GE-180 has shown higher selectivity for TSPO than 11 C-PK11195 (10).…”

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confidence: 99%

“…1) is the lead compound from a new series of tricyclic indoles, which have been shown to have a high affinity for TSPO (10). According to a preliminary in vitro and biodistribution study, 18 F-GE-180 has shown higher selectivity for TSPO than 11 C-PK11195 (10). However, no direct comparison has been made of the relative sensitivities of these 2 different TSPO radiotracers in a proven model of neuroinflammation.…”

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Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers¹¹C-(R)-PK11195 and¹⁸F-GE-180

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[18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18kDa (TSPO)

Cited by 120 publications

References 15 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

Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers¹¹C-(R)-PK11195 and¹⁸F-GE-180

Bischler Indole Synthesis

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[18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18kDa (TSPO)

Cited by 120 publications

References 15 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

Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers11C-(R)-PK11195 and18F-GE-180

Bischler Indole Synthesis

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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

Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers¹¹C-(R)-PK11195 and¹⁸F-GE-180