Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers

@article{Ettrup2010RadiosynthesisAI,
  title={Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers},
  author={Anders Ettrup and Martin Hansen and Martin A. Santini and James Paine and Nic Gillings and Mikael Palner and Szabolcs Lehel and Matthias Manfred Herth and Jacob Madsen and Jesper L. Kristensen and Mikael Begtrup and Gitte Moos Knudsen},
  journal={European Journal of Nuclear Medicine and Molecular Imaging},
  year={2010},
  volume={38},
  pages={681-693}
}
PurposePositron 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… 
Preclinical Safety Assessment of the 5-HT2A Receptor Agonist PET Radioligand [11C]Cimbi-36
TLDR
Administration of tracer doses of [11C]Cimbi-36 does not seem to be associated with unusual radiation burden or adverse clinical effects, and the estimated absorbed radiation dose to human target organs did not exceed safety levels.
Synthesis, radiofluorination, and preliminary evaluation of the potential 5-HT2A receptor agonists [18 F]Cimbi-92 and [18 F]Cimbi-150.
TLDR
A 2-step, 1-pot labelling methodology of 2 tracer candidates, synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs are reported.
Radiosynthesis and Biological Evaluation of [18F]R91150, a Selective 5-HT2A Receptor Antagonist for PET-Imaging.
TLDR
Autoradiographic studies with [18F]R91150 in rat brain slices revealed the typical uptake pattern of 5-HT2A receptor ligands, and the total synthesis time was reduced to 60 min.
Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions
TLDR
The biodistribution of Cimbi-36 (and its metabolites) may also help to shed light on the toxic effects of 25B-NBOMe when used in pharmacological doses in recreational settings.
Synthesis and evaluation of (18)F-labeled 5-HT2A receptor agonists as PET ligands.
Characterization of [11C]Cimbi-36 as an agonist PET radioligand for the 5-HT2A and 5-HT2C receptors in the nonhuman primate brain
The importance of small polar radiometabolites in molecular neuroimaging: A PET study with [11C]Cimbi-36 labeled in two positions
  • A. Johansen, H. D. Hansen, G. Knudsen
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2018
TLDR
It is shown that small polar radiometabolites can substantially decrease the signal-to- Background ratio of PET radioligands for neuroimaging, and it is found that [11C]Cimbi-36 has a better signal- to-background ratio, and thus will be more sensitive to changes in 5-HT2A receptor levels in the brain.
Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36
  • A. Ettrup, Sophie da Cunha-Bang, G. Knudsen
  • Biology, Medicine
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2014
TLDR
Cimbi-36 is described as the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain.
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11C-CIMBI-5 is a promising tool for investigation of 5-HT2A agonist binding in the living human brain and has a sufficient target-to-background ratio for future clinical use and is displaceable by ketanserin in both rats and pigs.
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Suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve the chances of successfully imaging endogenous neurotransmitters in the future.
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