In vivo biodistribution of a radiotracer for imaging serotonin-1A receptor sites with PET:[11C]LY274601

Life Sci. 1998;63(17):1533-42. doi: 10.1016/s0024-3205(98)00420-2.

Abstract

LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg/kg, s.c.), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocampus CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2-2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / chemistry
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Autoradiography
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Half-Life
  • Mice
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / pharmacokinetics*
  • Tetrahydronaphthalenes / pharmacology*
  • Tissue Distribution
  • Tomography, Emission-Computed / methods

Substances

  • LY 274601
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Tetrahydronaphthalenes
  • 8-Hydroxy-2-(di-n-propylamino)tetralin