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Flutriciclamide (18F-GE180) PET: first in human PET study of novel 3rd generation in vivo marker of human translator protein

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  • Zhen Fan
  • Valeria Calsolaro
  • Rebecca Áilish Atkinson
  • Grazia D Femminella
  • Adam Waldman
  • Christopher Buckley
  • William Trigg
  • David James Brooks
  • Rainer Hinz
  • Paul Edison

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    Rights statement: This research was originally published in JNM. Zhen Fan*,1, Valeria Calsolaro*,1, Rebecca A. Atkinson1, Grazia D. Femminella1, Adam Waldman1, Christopher Buckley2, William Trigg2, David J. Brooks1,3, Rainer Hinz4 and Paul Edison. Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein . JNM. 2016;vol 57:1753-1759 . © by the Society of Nuclear Medicine and Molecular Imaging, Inc.

    Accepted author manuscript, 993 KB, PDF document

Original languageEnglish
JournalJournal of Nuclear Medicine
Early online date3 Jun 2016
DOIs
Publication statusPublished - 1 Nov 2016

Abstract

Neuroinflammation is associated with neurodegenerative disease. PET (positron emission tomography) radioligands targeting the 18 kDa translocator protein (TSPO) has 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 third generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modelling strategies for (18)F-GE180 PET in (older) healthy controls (HC).

METHODS: Ten HC, six TSPO high affinity binders (HABs) and four mixed affinity binders (MABs), were recruited. All subjects had detailed neuropsychological tests, MRI and a 210 min (18)F-GE180 dynamic PET/CT scan using metabolite corrected arterial plasma input function. We evaluated five different kinetic models: irreversible and reversible two-tissue compartment models, a reversible one-tissue model and two models with an extra irreversible vascular compartment. The optimum scan length was investigated based on 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. Using the kinetic model, the volume of distribution (VT) was 0.17 in HABs and 0.12 in MABs. The model that best represented brain (18)F-GE180 kinetics across regions was the reversible two-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 kinetic model, which could be used for voxel-wise analysis.

CONCLUSION: We report for the first time 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 Logan approach could be used to generate parametric maps. While these control subjects have shown relatively low VT, the methodology presented here forms the basis for quantification for future PET studies using (18)F-GE180 in different pathologies.

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