Quantification of 5-HT1A receptors in human brain using p-MPPF kinetic modelling and PET

Abstract

Serotonin-1A (5-HT(1A)) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N-(2"-pyridinyl)- p-[(18)F]fluorobenzamido] ethyl] piperazine ( p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT(1A) receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT(1A) receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT(1A) receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT(1A) receptor human studies.

The physiology of moral sentiments

“…This is how it works: a positive social stimulus causes OT release that potentiates the discharge of midbrain DA (Liu and Wang, 2003;Petersson et al, 1999). At the same time, OT release causes synaptic SERT to rise (Pfister and Muir, 1989), producing calmness and a positive effect on mood by binding to 5-HT1A (serotonin) receptors in the temporal cortex and prefrontal cortex (Sanabria-Bohórquez et al, 2002). More Fig.…”

Synthesis and preliminary in vivo evaluation of 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide, a potential PET radioligand for the 5‐HT1A receptor

“…1 5 ) which is capable of delineating the 5-HT 1A receptor in human brain. 6 [Carbonyl- 11 ) seems to possess even better in vivo properties as demonstrated by its significantly higher brain radioactivity signal providing improved imaging statistics, advantages in biomathematic modeling and the preclusion of [ 11 C]-DWAY as a metabolite interfering with PET measurements. 8 Because of the better nuclear properties of the 18 F isotope and the more reliable radiosynthetic procedures, 18 F labelled WAY100635 analogs were rapidly developed with […”

“…[9][10][11] The lower affinity of MPPF for the 5-HT 1A receptor in comparison to WAY100635 could make this ligand sensitive to endogenous serotonin concentration which could enable us to detect differences in serotonin release.…”

“…3,4 The nuclear imaging modalities PET (positron emission tomography) and SPECT (single photon emission computed tomography) offer the unique opportunity to study in vivo and non-invasively, the 5-HT 1A receptor, using a selective radioligand. At the moment, only 5-HT 1A receptor PET tracers are available with the lead component [carbonyl- 11 …”

Synthesis and biological evaluation of 99mTc-HEDTA/HYNIC-MPP4 complex for 5-HT1A receptor imaging

“…In the past few years, PET agents for imaging 5-HT 1A receptor have been studied extensively [1,[6][7][8][9][10][11][12][13][14] , such as 11 Clabeled N- (2-[4-(2-methoxyphenyl) -1-piperazinyl] ethyl-N- (2-pyridinyl) cyclohexanecarboxamide [ 11 C-WAY-100635] [6,13] , 4-(2′-methoxyphenyl)-1-[2′-(N-2′′-pyridinyl) -p-18 F-fluorobenzamido] ethylpiperazine [ 18 F-MPPF] [9,15] , 18 F-labeled trans-4-fluoro-N- (2-[4-(2-methoxyphenyl) piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxam ide [ 18 F-FC WAY]) [14] , and N-{2- [4-(2-methoxyphenyl) piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-18 F-fluoro-methylcyclohexane)carboxamide ( 18 F-MEFWAY) [16] . Among those PET tracers, a fluoro-analogue of WAY 100635 ([ 18 F]p-MPPF) has been investigated extensively and received the most concerns due to its positive results obtained in animals and human beings [1,11,[17][18][19] . [ 18 F] p-MPPF was developed by Shiue et al [15] in 1997 and then the procedure was modified by Le Bars et al [9] .…”