Preclinical investigation of the effect of stress on the binding of [18F]F13640, a 5-HT1A radiopharmaceutical

Abstract

Background

[¹⁸F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT_1A receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT_1A receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [¹⁸F]FDG and then proceeded to test for effects of this model on the cerebral binding of [¹⁸F]F13640, a 5-HT_1A receptors PET radiopharmaceutical.

Methods

Four groups of male Sprague-Dawley were used to identify the optimal model: “stressed group” (n = 10), “post-traumatic stress disorder (PTSD) group” (n = 9) and “restraint group” (n = 8), compared with a control group (n = 8). All rats performed neuroimaging [¹⁸F]FDG μPET-CT to decipher which model was the most appropriate to test effects of stress on radiotracer binding. Subsequently, a group of rats (n = 10) underwent two PET imaging acquisitions (baseline and PTSD condition) using the PET radiopharmaceutical [¹⁸F]F13640 to assess influence of stress on its binding. Voxel-based analysis was performed to assess [¹⁸F]FDG or [¹⁸F]F13640 changes.

Results

In [¹⁸F]FDG experiments, the PTSD group showed a pattern of cerebrometabolic activation in various brain regions previously implicated in stress (amygdala, perirhinal cortex, olfactory bulb and caudate). [¹⁸F]F13640 PET scans showed increased radiotracer binding in the PTSD condition in caudate nucleus and brainstem.

Conclusions

The present study demonstrated stress-induced cerebrometabolic activation or inhibition of various brain regions involved in stress model. Applying this model to our radiotracer, [¹⁸F]F13640 showed few influence of stress on its binding. This will enable to rule out any confounding effect of stress during imaging studies.