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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-02-2020 | Multiple Sclerosis | Original Article

The P2X₇ receptor tracer [¹¹C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study

Authors: Marloes H. J. Hagens, Sandeep S. V. Golla, Bieneke Janssen, Danielle J. Vugts, Wissam Beaino, Albert D. Windhorst, James O’Brien-Brown, Michael Kassiou, Robert C. Schuit, Lothar A. Schwarte, Helga E. de Vries, Joep Killestein, Frederik Barkhof, Bart N. M. van Berckel, Adriaan A. Lammertsma

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2020

Abstract

Purpose

The novel PET tracer [¹¹C]SMW139 binds with high affinity to the P2X₇ receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [¹¹C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify in vivo neuroinflammation in RRMS.

Methods

Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [¹¹C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.

Results

The optimal model for describing [¹¹C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k₄ fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (V_T) and binding potential (BP_ND) in RRMS compared with HC in normal appearing brain regions. BP_ND in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased V_T was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional V_T and BP_ND values.

Conclusions

This first in-man study demonstrated that uptake of [¹¹C]SMW139 can be quantified with PET using BP_ND as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.

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Title: The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study
Authors: Marloes H. J. Hagens
Sandeep S. V. Golla
Bieneke Janssen
Danielle J. Vugts
Wissam Beaino
Albert D. Windhorst
James O’Brien-Brown
Michael Kassiou
Robert C. Schuit
Lothar A. Schwarte
Helga E. de Vries
Joep Killestein
Frederik Barkhof
Bart N. M. van Berckel
Adriaan A. Lammertsma
Publication date: 01-02-2020
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Sclerosis
Positron Emission Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04550-x

At a glance: The STEP trials

Springer Medicine

The P2X₇ receptor tracer [¹¹C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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