Abstract
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Objectives Disruptions in the serotonin 5-HT1A receptor system are implicated in affective and memory dysfunction in many neuropsychiatric illnesses. Preliminary studies suggest MEFWAY (MEF) will offer significant improvements in experimental ease and quantitative accuracy for PET studies of this system. The objective of this work is to compare the in vivo kinetics of 5-HT1A antagonists [F-18]MEF and [F-18]MPPF in the rhesus monkey.
Methods Dynamic microPET scans of MEF and MPPF were acquired on 2 anesthetized rhesus monkeys. Arterial blood samples were drawn throughout the 2 hr scan and parent compound was assayed. TACs were obtained from the identically processed images for the regions of the anterior cing(AC), hippocampus complex(HP) and raphe nuclei(RN) for specific binding and the cerebellum(CBM) as a reference region.
Results In the arterial plasma, both radiotracers cleared from the plasma at a similar rate, with a slow component of 0.0088 and 0.0093 min-1 for MEF and MPPF. The CBM to plasma ratios plateaued at 3:1 for MEF and 1.5:1 for MPPF. The target to cerebellum ratios were (MEF and MPPF): AC– 17 and 6.0, HP– 15 and 7.0, RN– 7.0 and 3.3. In the AC, pseudoequil was reached at 60 min for MEF and 40 min for MPPF. MEF images also revealed high uptake (>3:1) in the regions of the temporal, frontal and cingulate cortex which were not evident with MPPF.
Conclusions MEFWAY yields a significant improvement in target to reference uptake compared to MPPF, thus showing promise as a 5-HT1A biomarker with increased sensitivity for studying the 5-HT1A system.
Research Support AA017706,AG030524,AA12277
- © 2009 by Society of Nuclear Medicine