Epilepsy: TSPO imaging
Research type
Research Study
Full title
Epilepsy imaging with 11C-PBR28 PET: assessment of variability
IRAS ID
210640
Contact name
M Johnson
Contact email
Sponsor organisation
Joint Research Office
Eudract number
n/a
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
In this study, we are using a scanning technique (called PET) to measure the amount of a certain protein (called TSPO) that is present in the brains of people with epilepsy.
TSPO levels rise when the brain is slightly inflamed, so this scanning technique will allow us to measure how much inflammation there is in the brain of people with epilepsy. This is important, because we know that inflammation helps to cause epilepsy in some people (but not all people). The reason this scanning technique could be useful, therefore, is because it could help us identify which people with epilepsy have inflammation and hence which people might benefit from anti-inflammatory treatment.
We already know (from other studies) that the levels of TSPO are, on average, higher in the brains of people who have epilepsy than people who don’t. However, we don’t know much more about it yet and this is why we are doing the study. We have 2 main questions.
1) If someone with epilepsy is scanned twice over a period of a few weeks, does the level of inflammation stay quite constant, or does it chop and change?
2) How varied is the level of inflammation between patients? Eg do all patients have quite similar levels of inflammation, or do some have normal levels and do others with very high levels?
We will be recruiting people with epilepsy from clinics at Imperial College and University College London hospitals. We will invite them to Hammersmith Hospital for a screening visit and then invite them back for a study visit to perform a PET scan. Some people will be invited for a 3rd time (around 2 months later) for a second scan. The PET scans will take place at the Imanova Centre for Imaging Sciences, also at the Hammersmith Hospital.
Summary of Results
Translocator-protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here we examine test retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used an endpoint in clinical trials for epilepsy.
Methods
Five subjects with epilepsy were scanned twice – on average 8 weeks apart – using a TSPO targeting radioligand, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 male) previously studied healthy volunteers.
Results
The mean (± SD) of the volume of distribution (VT), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest is 4.49 ± 1.54, versus 5.89 ±1.23 in healthy volunteers. The bias between test and retest in asymmetry index as % was small (-1.5%) and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, VT of [11C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region.
Conclusion
When using TSPO PET in epilepsy patients with hippocampal sclerosis, inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in VT represents the clinic outcome.REC name
London - West London & GTAC Research Ethics Committee
REC reference
16/LO/1800
Date of REC Opinion
24 Nov 2016
REC opinion
Further Information Favourable Opinion