Abstract

BackgroundOver 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.MethodsAll 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.ResultsThe 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.ConclusionThe 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.

Highlights

  • IntroductionPositron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as positron emission tomography (PET) can visualise molecular processes, such as neuroinflammation, in vivo

  • 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

  • In patients with a relapsing-remitting disease course, radiological monitoring is based on the development of new MS lesions on T2-weighted Magnetic resonance imaging (MRI) and the presence of gadolinium-enhancing lesions on T1-weighted MRI, demonstrating disruption of the blood-brain barrier which is indicative of active neuroinflammation [3]

Read more

Summary

Introduction

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. In patients with a relapsing-remitting disease course, radiological monitoring is based on the development of new MS lesions on T2-weighted MRI and the presence of gadolinium-enhancing lesions on T1-weighted MRI, demonstrating disruption of the blood-brain barrier which is indicative of active neuroinflammation [3] These focal lesions as seen on MRI cannot fully explain the neurological and cognitive deficits in patients with MS [4].

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call