Journal ArticleDOI
Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers.
Anders Ettrup,Martin Hansen,Martin Hansen,Martin A. Santini,James Paine,James Paine,Nic Gillings,Mikael Palner,Szabolcs Lehel,Matthias M. Herth,Jacob Madsen,Jesper L. Kristensen,Jesper L. Kristensen,Mikael Begtrup,Mikael Begtrup,Gitte M. Knudsen +15 more
TLDR
The largest target-to-background binding ratio was found for [11C]Cimbi-36 which also had a high brain uptake compared to its analogues, and is currently the most promising candidate for investigation of 5-HT2A receptor agonist binding in the living human brain with PET.Abstract:
Positron emission tomography (PET) imaging of serotonin 2A (5-HT2A) receptors with agonist tracers holds promise for the selective labelling of 5-HT2A receptors in their high-affinity state. We have previously validated [11C]Cimbi-5 and found that it is a 5-HT2A receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [11C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT2A receptor agonist PET tracers in the pig brain. Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT2A receptor binding, cortical nondisplaceable binding potentials (BPND) were calculated using the simplified reference tissue model with the cerebellum as a reference region. After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT2A receptor distribution. The largest target-to-background binding ratio was found for [11C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [11C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT2A receptor selectivity in vivo. [11C]Cimbi-82 and [11C]Cimbi-21 showed lower cortical BPND, while [11C]Cimbi-27, [11C]Cimbi-29, [11C]Cimbi-31 and [11C]Cimbi-88 gave rise to cortical BPND similar to that of [11C]Cimbi-5. [11C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT2A receptor agonist binding in the living human brain with PET.read more
Citations
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Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).
TL;DR: The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α1 receptor interactions.
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5-HT radioligands for human brain imaging with PET and SPECT.
TL;DR: The development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radiolIGands for human brain imaging.
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25C-NBOMe – New potent hallucinogenic substance identified on the drug market
TL;DR: Analytical properties of a new hallucinogenic substance identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine].
Journal ArticleDOI
The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample
TL;DR: The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet.
References
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Simplified Reference Tissue Model for PET Receptor Studies
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Journal ArticleDOI
Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior
Javier González-Maeso,Noelia V. Weisstaub,Mingming Zhou,Pokman Chan,Lidija Ivic,Rosalind L. Ang,Alena Lira,Maria Bradley-Moore,Yongchao Ge,Qiang Zhou,Stuart C. Sealfon,Jay A. Gingrich +11 more
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Journal ArticleDOI
Impact of image-space resolution modeling for studies with the high-resolution research tomograph.
F.C. Sureau,Andrew J. Reader,Claude Comtat,Claire Leroy,Maria-Joao Ribeiro,Irène Buvat,Regine Trebossen +6 more
TL;DR: In high-resolution PET, RM during reconstruction improves quantitative accuracy by reducing the partial-volume effects and improving spatial resolution in clinical images reconstructed with RM.