In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET.

Abstract:

BACKGROUND:Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with high affinity to the 18-kDa translocator-protein (TSPO), which is mainly expressed on activated microglia. The aim of this proof of concept study was to evaluate this in vivo marker of neuroinflammation in primary and secondary progressive MS. METHODS:All subjects were genotyped for the rs6971 polymorphism within the TSPO gene, and low-affinity binders were excluded from participation in this study. Eight patients with progressive MS and seven age and genetic binding status matched healthy controls underwent a 60 min dynamic PET scan using [18F]DPA714, including both continuous on-line and manual arterial blood sampling to obtain metabolite-corrected arterial plasma input functions. RESULTS:The optimal model for quantification of [18F]DPA714 kinetics was a reversible two-tissue compartment model with additional blood volume parameter. For genetic high-affinity binders, a clear increase in binding potential was observed in patients with MS compared with age-matched controls. For both high and medium affinity binders, a further increase in binding potential was observed in T2 white matter lesions compared with non-lesional white matter. Volume of distribution, however, did not differentiate patients from healthy controls, as the large non-displaceable compartment of [18F]DPA714 masks its relatively small specific signal. CONCLUSION:The TSPO radioligand [18F]DPA714 can reliably identify increased focal and diffuse neuroinflammation in progressive MS when using plasma input-derived binding potential, but observed differences were predominantly visible in high-affinity binders.

journal_name

J Neuroinflammation

authors

Hagens MHJ,Golla SV,Wijburg MT,Yaqub M,Heijtel D,Steenwijk MD,Schober P,Brevé JJP,Schuit RC,Reekie TA,Kassiou M,van Dam AM,Windhorst AD,Killestein J,Barkhof F,van Berckel BNM,Lammertsma AA

doi

10.1186/s12974-018-1352-9

subject

Has Abstract

pub_date

2018-11-13 00:00:00

pages

314

issue

1

issn

1742-2094

pii

10.1186/s12974-018-1352-9

journal_volume

15

pub_type

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