A Reduced Extracellular Serotonin Level Increases the 5-HT1A PET Ligand 18F-MPPF Binding in the Rat Hippocampus

Journal of Nuclear Medicine

Latifa Rbah¹  Fabrice Giacomelli¹  Didier Le Bars¹  Bernard Renaud¹  Luc Zimmer¹ 

关键词: serotonin receptors;    p-ethynylphenylalanine;    4;    2′-(methoxyphenyl)-1-[2′-(N-2″-pyridinyl)-p-fluorobenzamido]-ethylpiperazine;    serotonin;    microdialysis;    β-microprobe;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

4,2′-(Methoxyphenyl)-1-[2′-(N-2″-pyridinyl)-p-fluorobenzamido]ethylpiperazine (18F-MPPF) is a radiotracer used in clinical PET studies for the visualization of serotonin-1A (5-HT1A) receptors. In a previous study, we demonstrated that a rapid enhancement of extracellular serotonin concentrations influences 18F-MPPF-specific binding. Because endogenous serotonin is significantly decreased in some pathologies, the aim of this study was to determine whether 18F-MPPF is sensitive to depletion of this neurotransmitter. Methods: Using the β-microprobe, an original β+-sensitive intracerebral probe, and microdialysis, the effect of decreased serotonin on the specific binding of 18F-MPPF to 5-HT1A receptors was investigated in the hippocampus of the anesthetized rat. Extracellular serotonin was pharmacologically decreased in the hippocampus after a single injection of p-ethynylphenylalanine ([p-EPA] 5 mg/kg), a new tryptophan hydroxylase inhibitor. Results: Our results showed that the 18F-MPPF-specific binding was significantly enhanced after the decrease of extracellular serotonin. These results were confirmed by the 18F-MPPF distribution in cerebral tissues (hippocampus-to-cerebellum ratio) and by the decrease of the extracellular 18F-MPPF collected in hippocampal dialysates. Conclusion: This study further supports the view that 18F-MPPF binding potential is increased in the hippocampus if the endogenous serotonin is pharmacologically decreased after a p-EPA injection. This phenomenon will be an additional factor in the interpretation of the results from 18F-MPPF clinical PET studies.

【 授权许可】

Unknown