Testing PET-[ ¹¹ C]ABP688 as a tool to quantify glutamate release in vivo

Area of Science:

• Neuroscience
• Radiochemistry
• Addiction Research

Background:

• Glutamate is crucial for neuroplasticity and addiction.
• Measuring glutamate release in the human brain is challenging.
• Metabotropic glutamate type 5 (mGlu5) receptors are potential targets for PET imaging.

Purpose of the Study:

• To evaluate [11C]ABP688 PET as a method for quantifying glutamate release in vivo.
• To investigate ethanol's effect on glutamate release in rats and humans.
• To assess the impact of stress on glutamate turnover in humans.

Main Methods:

• Rats: Microdialysis and [11C]ABP688 microPET imaging.
• Humans: Positron Emission Tomography (PET) with [11C]ABP688 and Magnetic Resonance Spectroscopy (MRS).
• Pharmacological challenges: Ethanol administration in rats, laboratory stressor in humans.

Main Results:

• Ethanol administration increased calcium-dependent glutamate release in rat ventral striatum.
• [11C]ABP688 binding decreased concurrently with glutamate release in anesthetized rats, but without significant correlation.
• Human studies showed stress-induced changes in mood, sympathetic activation, and Glx/Cr levels, but no significant changes in [11C]ABP688 binding.
• No significant correlation was found between glutamate turnover and [11C]ABP688 binding in humans.

Conclusions:

• The study documented ethanol-induced glutamate release and associated changes in [11C]ABP688 binding in rats.
• The PET [11C]ABP688 method did not prove effective for quantifying moderate glutamate release changes in humans under stress.
• Highly controlled conditions are necessary for PET measures of mGlu5 receptors.