MicroPET imaging of 5-HT1A receptors in rat brain: a test-retest [18F]MPPF study

Purpose Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [F-18] MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A 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-HT1A receptors with [F-18] MPPF thus represents a promising avenue for investigating 5-HT1A receptor function in rat.