[18F]RS-127445 radiosynthesis and evaluation as a 5-HT2B receptor PET radiotracer in rat brain

Bioorg Med Chem Lett. 2024 Nov 1:112:129933. doi: 10.1016/j.bmcl.2024.129933. Epub 2024 Aug 27.

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in many physiological and pathological mechanisms through its numerous receptors. Among these, the 5-HT2B receptor is known to play a key role in multiple brain disorders but remains poorly understood. Positron emission tomography (PET) can contribute to a better understanding of pathophysiological mechanisms regulated by the 5-HT2B receptor. To develop the first PET radiotracer for the 5-HT2B receptor, RS-127445, a well-known 5-HT2B receptor antagonist, was labeled with fluorine-18. [18F]RS-127445 was synthesized in a high radiochemical purity and with a good molar activity and radiochemical yield. Preliminary PET scans in rats showed good brain penetration of [18F]RS-127445. However, competition experiments and in vitro autoradiography showed high non-specific binding, especially to brain white matter.

Keywords: 5-HT(2B) receptor; PET imaging; RS-127445.

MeSH terms

  • Animals
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Fluorine Radioisotopes* / chemistry
  • Fluorobenzenes
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Positron-Emission Tomography*
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / chemistry
  • Rats
  • Receptor, Serotonin, 5-HT2B* / metabolism
  • Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Antagonists / chemistry
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT2B
  • Fluorine-18
  • Piperidines
  • Serotonin 5-HT2 Receptor Antagonists
  • volinanserin
  • Fluorobenzenes