Imaging the glutamate system

By Dr Matt Wilkinson

- Last updated on GMT

Related tags: Positron emission tomography

Researchers from the Karolinska Institutet in Stockholm, Sweden and
AstraZeneca have developed the first method that allows the
glutamate system to be studied in living people.

The glutamate system is the largest neurotransmitter system, and there is a large body of pharmacological data that suggests the system may play an important role in schizophrenia. However, until now it has not been possible to capture images of the glutamate system. The new system works by injecting a carbon-11 labelled radio-tracer molecule that specifically binds to the glutamate receptors in the brain which can then be imaged using positron-emission topography (PET). "The glutamate system is the biggest neurotransmitter system in the brain, more neurons use glutamate to signal to other neurons than any other system in the brain,"​ said Professor Lars Farde of Karolinska Institutet and AstraZeneca. "From an academic and clinical perspective the glutamate system is of central interest in schizophrenia and there is a strong glutamate hypothesis on the pathophysiology of schizophrenia and a central interest in epilepsy, anxiety disorders as well as several other disorders." ​ Professor Farde continued by explaining that glutamate can bind to any of 17 different receptors in the brain, and despite this rich availability of potential targets there are no other good ligands available for PET imaging. "From a pharmacological perspective several of the proteins or receptors are considered as potential drug targets and I would guess that all big Pharma consider targets of the glutamate system in their development system,"​ said Professor Farde. PET imaging systems study the decay of short-lived radioactive tracer atoms that emit a positron as they decay. The positrons emitted then react with electrons to produce a pair of gamma photons that can be detected by a ring of photomultiplier tubes or silicon avalanche photodiodes. Because the photons are emitted at 180º from each other it is possible to calculate the location of the molecule and provide 3D images that track the movements of signalling substances in the body. One of the major limitations of PET imaging is that the isotopes have short half-lives the radionuclide tracer atoms need to be produced in a cyclotron, incorporated into the tracer molecule and delivered into the subject before the radionuclide decays. This especially crucial for carbon-11 which has a half-life of 20 minutes, meaning that the researchers have to make the tracer fresh each time they want to use it, sometimes several times a day. "The advantage of carbon-11 is that you can do several PET measurements in the same subject on the same day, for instance you can examine a subject at baseline and after various treatment conditions because it decays within two hours,"​ said Farde. The group are currently conducting animal studies, and are looking at gaining approval from the radiation safety committee to approve a human study.

Related topics: Preclinical Research

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