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MicroPET imaging of 5-HT 1A receptors in rat brain: a test-retest [18F]MPPF study
Nicolas Aznavour1, Chawki Benkelfat, Paul Gravel
1Department of Psychiatry, McGill University, Montreal, QC, Canada. nicolas.aznavour@epfl.ch
Purpose:
Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [(18)F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in different regions of animal and human brain, including that of 5-HT(1A) autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems).
Methods:
Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model.
Results:
Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei.
Conclusions:
MicroPET brain imaging of 5-HT(1A) receptors with [(18)F]MPPF thus represents a promising avenue for investigating 5-HT(1A) receptor function in rat.
Insights
MicroPET imaging with [(18)F]MPPF successfully measured serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential in rat brains. This technique shows promise for future research into 5-HT(1A) receptor function in rats.
Area of Science:
- Neuroscience
- Radiochemistry
- Pharmacology
Background:
- Positron emission tomography (PET) enables measurement of serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential.
- Previous studies utilized PET imaging in various species, including humans, to assess 5-HT(1A) receptor distribution.
Purpose of the Study:
- To evaluate the feasibility of obtaining quantitative microPET imaging data for 5-HT(1A) receptors in the rat brain.
- To determine if [(18)F]MPPF binding potential could be measured in specific rat brain regions using microPET.
Main Methods:
- MicroPET scans were performed on isoflurane-anesthetized rats (n=18).
- Data were co-registered with MRI, and binding potential was estimated using a simplified reference tissue model.
- Test-retest variability was assessed in multiple brain regions.
Main Results:
- Binding potential values for various rat brain regions (e.g., hippocampus, amygdala, raphe nuclei) were obtained.
- These values were comparable to those reported in other species using PET.
- Test-retest variability was generally below 20%, indicating good reproducibility.
Conclusions:
- MicroPET imaging with [(18)F]MPPF is a viable method for quantifying 5-HT(1A) receptor binding potential in rats.
- This technique offers a promising tool for studying 5-HT(1A) receptor function in preclinical rat models.
