Quantification of 5-HT(1A) receptors in human brain using p-MPPF kinetic modelling and PET

Eur J Nucl Med Mol Imaging. 2002 Jan;29(1):76-81. doi: 10.1007/s00259-001-0684-2. Epub 2001 Nov 22.

Abstract

Serotonin-1A (5-HT(1A)) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N-(2"-pyridinyl)- p-[(18)F]fluorobenzamido] ethyl] piperazine ( p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT(1A) receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT(1A) receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT(1A) receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT(1A) receptor human studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminopyridines* / pharmacokinetics
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Cerebellum / diagnostic imaging
  • Cerebellum / metabolism
  • Female
  • Fluorine Radioisotopes* / pharmacokinetics
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism
  • Humans
  • Ligands
  • Male
  • Models, Biological
  • Piperazines* / pharmacokinetics
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin, 5-HT1
  • Tomography, Emission-Computed*

Substances

  • Aminopyridines
  • Fluorine Radioisotopes
  • Ligands
  • Piperazines
  • Radiopharmaceuticals
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • 4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine