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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2011

01-04-2011 | Original Article

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

Authors: Anders Ettrup, Martin Hansen, Martin A. Santini, James Paine, Nic Gillings, Mikael Palner, Szabolcs Lehel, Matthias M. Herth, Jacob Madsen, Jesper Kristensen, Mikael Begtrup, Gitte M. Knudsen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2011

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

[11C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT2A receptor agonist binding in the living human brain with PET.
Appendix
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Metadata
Title
Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers
Authors
Anders Ettrup
Martin Hansen
Martin A. Santini
James Paine
Nic Gillings
Mikael Palner
Szabolcs Lehel
Matthias M. Herth
Jacob Madsen
Jesper Kristensen
Mikael Begtrup
Gitte M. Knudsen
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-010-1686-8

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