The Translocator Protein (TSPO) is a protein which reaches very high levels when there is inflammation in the brain. Recently, radioligands have been developed which attach to the TSPO (a radioligand is a drug which has been tagged with radioactivity). Using positron emission tomography (PET) imaging, the radioligand can be detected following injection into a patient. However, it is difficult to accurately measure the amount of TSPO using PET at the moment. This is because the brain does not have a "reference region" for TSPO (ie an area in the brain with no TSPO at all). "Reference regions" are very useful to help work out how much of a PET signal represents "specific binding" (of the radioligand to the target of interest), and how much represents "non specific binding" (of the radioligand to many other structures which are not of interest). In the absence of a reference region, non specific binding can be estimated by giving a drug which binds to the TSPO. The drug prevents the radioligand binding the TSPO and (in a manner of speaking) "creates" a temporary reference region so non specific binding can be measured. To do this, we will use XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor) to bind TSPO and block binding of the PET ligand ([11C]PBR28), a TSPO ligand from the phenoxyarlyacetamide class. Most TSPO PET studies (and in one of our previous studies approved by West London REC) quantify the signal using a ratio of specific binding in the brain to radioactivity in the blood. This requires arterial line insertion which is burdensome for subjects, and increases variability. In this study we aim to determine the ratio of specific binding in the brain to nonspecific binding in the brain by using the temporary reference region. For more accuracy the participants will repeat the scanning procedure so determine test-retest variability of the amount of TSPO.
Description: Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.Measure: TSPO Binding Status Time: Baseline/Screening visit
Description: Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients. Subjects will receive a baseline 11C-PBR28 scan, and then a repeat scan following an oral dose of 90mg XBD173 (Emapunil). Both VT and BPND will be determined. Subjects will then return approximately 10 days later for a repeat of these procedures.Measure: To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients. Time: 1st and 2nd Study Visit (approximately 10 days after the 1st study visit)
Single Group Assignment
There is one SNP
Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.. To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.. Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients.