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.