Zhen Fan1, Valeria Calsolaro1, Rebecca A Atkinson1, Grazia D Femminella1, Adam Waldman1, Christopher Buckley2, William Trigg2, David J Brooks1,3, Rainer Hinz4, Paul Edison5. 1. Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, United Kingdom. 2. GE Healthcare, Grove Centre, Amersham, United Kingdom. 3. Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark; and. 4. Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom. 5. Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, United Kingdom paul.edison@imperial.ac.uk.
Abstract
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 (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-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 18F-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: 18F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (VT) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18F-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 VT highly consistent with VT 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 18F-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 VT, the methodology presented here forms the basis for quantification for future PET studies using 18F-GE180 in different pathologies.
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 (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-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 18F-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: 18F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (VT) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18F-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 VT highly consistent with VT 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 18F-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 VT, the methodology presented here forms the basis for quantification for future PET studies using 18F-GE180 in different pathologies.
Authors: Nathalie L Albert; Marcus Unterrainer; Matthias Brendel; Lena Kaiser; Markus Zweckstetter; Paul Cumming; Peter Bartenstein Journal: Eur J Nucl Med Mol Imaging Date: 2019-03-02 Impact factor: 9.236
Authors: Paolo Zanotti-Fregonara; Mattia Veronese; Belen Pascual; Robert C Rostomily; Federico Turkheimer; Joseph C Masdeu Journal: Eur J Nucl Med Mol Imaging Date: 2019-01-17 Impact factor: 9.236
Authors: M Unterrainer; D F Fleischmann; F Vettermann; V Ruf; L Kaiser; D Nelwan; S Lindner; M Brendel; V Wenter; S Stöcklein; J Herms; V M Milenkovic; R Rupprecht; J C Tonn; C Belka; P Bartenstein; M Niyazi; N L Albert Journal: Eur J Nucl Med Mol Imaging Date: 2019-09-05 Impact factor: 9.236
Authors: Nathalie L Albert; M Unterrainer; D F Fleischmann; S Lindner; F Vettermann; A Brunegraf; L Vomacka; M Brendel; V Wenter; C Wetzel; R Rupprecht; J-C Tonn; C Belka; P Bartenstein; M Niyazi Journal: Eur J Nucl Med Mol Imaging Date: 2017-08-19 Impact factor: 9.236