ECTRIMS eLearning

[18F]GE-180, a novel TSPO-PET tracer for visualization of inflammatory CNS-activity in MS
ECTRIMS Learn. Mahler C. 10/27/17; 202609; 246
Christoph Mahler
Christoph Mahler
Contributions
Abstract

Abstract: 246

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background: We used the novel 3rd Generation TSPO-Tracer [18F]GE-180 in positron-emission tomography (PET) to visualize inflammatory activity in the CNS in-vivo in patients with relapsing-remitting multiple sclerosis (RRMS). In the CNS the translocator-protein (TSPO) is expressed primarily by activated microglia and macrophages. Uptake of TSPO radioligands can therefore be used to non-invasively image neuroinflammation in patients. Recently, new TSPO tracers have been developed, which show higher selectivity and improved signal-to-noise ratios compared to 1st generation tracers such as [11C]PK11195.
Goals: The objective of this study was to compare [18F]GE-180 TSPO-PET imaging in RRMS to conventional contrast enhancement (CE) MRI as a direct measure of disease activity. We inquired, whether inflammatory lesions as a parameter of disease activity can be identified in [18F]GE-180 TSPO-PET tracer uptake and analyzed their temporospatial distribution in relation to CE lesions in concurrent and prior MRI.
Methods: Eleven patients with RRMS were included and underwent [18F]GE-180 TSPO-scans in a Siemens Biograph 64 PET/CT. A dose of 185MBq [18F]GE-180 was applied intravenously. Thereafter, 60-90 minutes summation images were acquired. Images were assessed by visual and quantitative analysis, where SUVRmean and SUVRmax of lesions were measured and normalized to reference tissue (frontal normal appearing cortex). 3T MRI was performed concurrently and, if available previous MRI data were used for temporal assessment of lesions.
Results: Inflammatory CNS lesions in MS can be visualized as hot-spots in [18F]GE-180 TSPO PET. 9/11 patients showed at least one hot-spot by visual analysis of PET images (SUVR 1.03-3.72; median 2.04) and a total of 50 hot-spots were identified. While 40 hot-spots showed concurrent contrast enhancement (CE) in MRI, we detected 10 TSPO hot-spots without CE. In previously acquired MRIs 4/7 hot-spots showed CE in a prior MRI, whereas 3/7 hot-spots showed no CE in prior MRI.
Conclusion: We demonstrated that via [18F]GE-180 TSPO-PET imaging inflammatory activity in MS lesions can be visualized with higher sensitivity and over longer time-spans compared to CE in MRI. Further, we showed that [18F]GE-180 TSPO-PET can be used to visualize inflammatory disease activity in the CNS in-vivo in RRMS patients with a signal to noise ratio exceeding that of 1st generation TSPO-tracers.
Disclosure:
C. Mahler: nothing to disclose
M. Unterrainer: nothing to disclose
L. Vomacka: nothing to disclose
S. Lindner: nothing to disclose
M. Brendel: nothing to disclose
A. Brunegraf: nothing to disclose
T. Kümpfel: nothing to disclose
R. Rupprecht: nothing to disclose
N. L. Albert: nothing to disclose
M. Kerschensteiner : In the past, M. Kerschensteiner has received honoraria for consulting and presentations from Biogen, Genzyme/Sanofi-Aventis, Med-
Day Pharmaceuticals, Novartis and TEVA, as well as research support
from Biogen and Genzyme/Sanofi-Aventis.
P. Bartenstein: nothing to disclose

Abstract: 246

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background: We used the novel 3rd Generation TSPO-Tracer [18F]GE-180 in positron-emission tomography (PET) to visualize inflammatory activity in the CNS in-vivo in patients with relapsing-remitting multiple sclerosis (RRMS). In the CNS the translocator-protein (TSPO) is expressed primarily by activated microglia and macrophages. Uptake of TSPO radioligands can therefore be used to non-invasively image neuroinflammation in patients. Recently, new TSPO tracers have been developed, which show higher selectivity and improved signal-to-noise ratios compared to 1st generation tracers such as [11C]PK11195.
Goals: The objective of this study was to compare [18F]GE-180 TSPO-PET imaging in RRMS to conventional contrast enhancement (CE) MRI as a direct measure of disease activity. We inquired, whether inflammatory lesions as a parameter of disease activity can be identified in [18F]GE-180 TSPO-PET tracer uptake and analyzed their temporospatial distribution in relation to CE lesions in concurrent and prior MRI.
Methods: Eleven patients with RRMS were included and underwent [18F]GE-180 TSPO-scans in a Siemens Biograph 64 PET/CT. A dose of 185MBq [18F]GE-180 was applied intravenously. Thereafter, 60-90 minutes summation images were acquired. Images were assessed by visual and quantitative analysis, where SUVRmean and SUVRmax of lesions were measured and normalized to reference tissue (frontal normal appearing cortex). 3T MRI was performed concurrently and, if available previous MRI data were used for temporal assessment of lesions.
Results: Inflammatory CNS lesions in MS can be visualized as hot-spots in [18F]GE-180 TSPO PET. 9/11 patients showed at least one hot-spot by visual analysis of PET images (SUVR 1.03-3.72; median 2.04) and a total of 50 hot-spots were identified. While 40 hot-spots showed concurrent contrast enhancement (CE) in MRI, we detected 10 TSPO hot-spots without CE. In previously acquired MRIs 4/7 hot-spots showed CE in a prior MRI, whereas 3/7 hot-spots showed no CE in prior MRI.
Conclusion: We demonstrated that via [18F]GE-180 TSPO-PET imaging inflammatory activity in MS lesions can be visualized with higher sensitivity and over longer time-spans compared to CE in MRI. Further, we showed that [18F]GE-180 TSPO-PET can be used to visualize inflammatory disease activity in the CNS in-vivo in RRMS patients with a signal to noise ratio exceeding that of 1st generation TSPO-tracers.
Disclosure:
C. Mahler: nothing to disclose
M. Unterrainer: nothing to disclose
L. Vomacka: nothing to disclose
S. Lindner: nothing to disclose
M. Brendel: nothing to disclose
A. Brunegraf: nothing to disclose
T. Kümpfel: nothing to disclose
R. Rupprecht: nothing to disclose
N. L. Albert: nothing to disclose
M. Kerschensteiner : In the past, M. Kerschensteiner has received honoraria for consulting and presentations from Biogen, Genzyme/Sanofi-Aventis, Med-
Day Pharmaceuticals, Novartis and TEVA, as well as research support
from Biogen and Genzyme/Sanofi-Aventis.
P. Bartenstein: nothing to disclose

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