(+)-p-([18F]fluorobenzyl)spirotrozamicol [(+)-[18F]spiro-FBT]: synthesis and biological evaluation of a high-affinity ligand for the vesicular acetylcholine transporter (VAChT)

Nucl Med Biol. 1999 Feb;26(2):189-92. doi: 10.1016/s0969-8051(98)00090-0.

Abstract

(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine*
  • Animals
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Evaluation Studies as Topic
  • Fluorine Radioisotopes
  • Macaca mulatta
  • Male
  • Membrane Transport Proteins*
  • Molecular Structure
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacokinetics
  • Synaptic Vesicles*
  • Tissue Distribution
  • Tomography, Emission-Computed
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*

Substances

  • 1'-(4-hydroxy-1-(4-fluorobenzyl)piperidin-3-yl)spiro(1H-indene-1,4'-piperidine)
  • Carrier Proteins
  • Fluorine Radioisotopes
  • Membrane Transport Proteins
  • Piperidines
  • Slc18a3 protein, rat
  • Spiro Compounds
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins
  • Acetylcholine