I2PETPG – Imidazoline2 Binding Site in patient group
Research type
Research Study
Full title
I2PETPG - Quantification and Localisation of Imidazoline2 Binding Sites in a group of participants diagnosed with Alzheimer’s Disease using 11C‑BU99008: a positron emission tomography study
IRAS ID
194836
Contact name
David Nutt
Contact email
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
The imdazoline2 binding site (I2BS) is known to reside on the mitochondrial membranes of astrocytes. Changes in the number of these binding sites in post-mortem human brain has implicated them in a range of psychiatric conditions such as depression and addiction, along with neurodegenerative disorders such as Alzheimer’s disease. Preclinical models have also demonstrated functional interactions with the opioid system, where I2BS ligands have been shown to affect tolerance to morphine and alleviate some of the morphine withdrawal syndrome in rats. The location of I2BS on glial cells and the possibility that they may in some way regulate glial fibrillary acidic protein have led to increased interest into the role of I2BS and I2BS ligands in conditions characterised by marked gliosis. The number of I2BS has been shown to increase in Alzheimer’s disease post-mortem, and it has also been suggested that I2BS may be a marker for the severity and malignancy of human glioblastomas. The lack of suitable tools has meant that information on I2BS in the brain has come from preclinical species or post-mortem studies. The recent development of 11C-BU99008 PET as a suitable tool to quantify I2BS in vivo, enables the direct quantification of I2BS availability and regional distribution in the living human brain. 11C-BU99008 has been extensively characterised in pre-clinical species and demonstrated to be a suitable research tool for the quantification of brain I2BS availability. We are coming to the conclusion of a successful study using 11C-BU99008 to quantify the regional brain availability of I2BS in the healthy human brain in vivo using positron emission tomography. Now we are seeking to complement this initial evaluation of the I2BS in healthy human brain with a similar study of I2BS in a patient group where it has been shown to change e.g. Alzheimer's disease (AD).
REC name
London - Chelsea Research Ethics Committee
REC reference
16/LO/0784
Date of REC Opinion
14 Jun 2016
REC opinion
Further Information Favourable Opinion