[14C]Serotonin uptake and [O-methyl-11C]venlafaxine kinetics in porcine brain

D. F. Smith, S. B. Hansen, L. Østergaard, A. D. Gee, E. Danielsen, K. Ishizu, D. Bender, P. H. Poulsen, A. Gjedde

Research output: Contribution to journalArticle

Abstract

As part of our program of developing PET tracers for neuroimaging of psychotropic compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured in vitro rates of serotonin uptake in synaptosomes prepared from selected regions of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O-methyl-11C]-labeled for PET. Synaptosomal studies showed that the active uptake of [14C]5-HT differed markedly between brain regions, with highest rates in hypothalamus, raphé region, and thalamus, and lowest rates in cortex and cerebellum. PET studies showed that the unidirectional rate of uptake of [O-methyl-11C]venlafaxine from blood to brain was highest in the hypothalamus, raphé region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under normal physiological conditions, the capillary permeability-surface area (PS) product for [O-methyl-11C]venlafaxine could not be estimated, because of complete flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred between the apparent partition volume of the radiotracer and the rate of active uptake of 5-HT in selected regions of the porcine brain. During hypercapnia, limitations of blood-brain transfer were observed, giving PS-products for water that were only ca. 50% higher than those of venlafaxine. Thus, under normal physiological conditions, the rate of uptake of venlafaxine from blood into brain is completely flow-limited.

Original languageEnglish (US)
Pages (from-to)633-638
Number of pages6
JournalNuclear Medicine and Biology
Volume28
Issue number6
DOIs
StatePublished - Jan 1 2001

    Fingerprint

Keywords

  • Antidepressant drug
  • Cerebral blood flow
  • PET pharmacokinetics
  • Porcine brain
  • Serotonin uptake
  • Venlafaxine

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Smith, D. F., Hansen, S. B., Østergaard, L., Gee, A. D., Danielsen, E., Ishizu, K., Bender, D., Poulsen, P. H., & Gjedde, A. (2001). [14C]Serotonin uptake and [O-methyl-11C]venlafaxine kinetics in porcine brain. Nuclear Medicine and Biology, 28(6), 633-638. https://doi.org/10.1016/S0969-8051(01)00230-X