In vitro characterization of 6-[18F]fluoro-A-85380, a high-affinity ligand for alpha4beta2* nicotinic acetylcholine receptors.

Journal Article (Journal Article)

Nicotinic acetylcholine receptors are involved in tobacco dependence and several other neuropathologies (e.g., Alzheimer's disease, Parkinson's disease), as well as in attention, learning, and memory. Performing in vivo imaging of these receptors in humans holds great promise for understanding their role in these conditions. Recently, three radiohalogenated analogs of 3-(2(S)-azetidinylmethoxy)pyridine (A- 85380) were used successfully for the in vivo visualization of alpha4beta2* nicotinic receptors in the human brain with PET/SPECT. Herein, we present the results of the in vitro characterization of one of these radioligands, 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)-pyridine (6-[18F]fluoro-A-85380), which is a fluoro-analog of the potent nonopioid analgesic ABT-594. In human postmortem cortical tissue, 6-[18F]fluoro-A-85380 reversibly binds with high affinity to a single population of sites (Kd = 59 pM at 37 degrees C, Bmax = 0.7 pmol/g tissue). The binding is fully reversible and is characterized at 37 degrees C by T(1/2assoc) = 2.2 min (at a ligand concentration of 39 pM) and by T(1/2dissoc) = 3.6 min. 6-Fluoro-A-85380 exhibits clear selectivity for alpha4beta2* over the other major mammalian nicotinic receptor subtypes: alpha7, alpha3beta4, and muscle-type. These results suggest that 6-[18F]fluoro-A-85380 is a promising radioligand for in vivo imaging of brain alpha4beta2* nicotinic receptors.

Full Text

Duke Authors

Cited Authors

  • Gündisch, D; Koren, AO; Horti, AG; Pavlova, OA; Kimes, AS; Mukhin, AG; London, ED

Published Date

  • February 2005

Published In

Volume / Issue

  • 55 / 2

Start / End Page

  • 89 - 97

PubMed ID

  • 15529332

International Standard Serial Number (ISSN)

  • 0887-4476

Digital Object Identifier (DOI)

  • 10.1002/syn.20096


  • eng

Conference Location

  • United States