• DOI:10.1007/s00259-010-1686-8
• Corpus ID: 12467684

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}
}

• A. Ettrup, Martin Hansen, +9 authors G. Knudsen
• Published 1 April 2011
• Biology, Chemistry, Medicine
• European Journal of Nuclear Medicine and Molecular Imaging

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 ways. Here, we present the in vivo validation of nine novel 5-HT2A receptor agonist PET tracers in the pig brain.MethodsEach 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.ResultsAfter 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.