In vitro evaluation of nicotinic acetylcholine receptors with 2-[18F]F-A85380 in Parkinson's disease

Schmaljohann, Jörn; Gündisch, Daniela; Minnerop, Martina; Bucerius, Jan; Joe, Alexius; Reinhardt, Michael; Guhlke, Stefan; Biersack, Hans-Jürgen; Wüllner, Ullrich

doi:10.1016/j.nucmedbio.2005.12.012

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 305-309, April 2006

In vitro evaluation of nicotinic acetylcholine receptors with 2-[¹⁸F]F-A85380 in Parkinson's disease

Jörn Schmaljohann
- Department of Neurology, University of Bonn, Germany
- Department of Nuclear Medicine, University of Bonn, Germany
- Corresponding author. Department of Nuclear Medicine, University of Bonn, 53105 Bonn, Germany. Tel.: +49 228 2879859; fax: +49 228 2879096.
Daniela Gündisch
- Department of Pharmaceutical Chemistry, University of Bonn, Germany
Martina Minnerop
- Department of Neurology, University of Bonn, Germany
Jan Bucerius
- Department of Nuclear Medicine, University of Bonn, Germany
Alexius Joe
- Department of Nuclear Medicine, University of Bonn, Germany
Michael Reinhardt
- Department of Nuclear Medicine, University of Bonn, Germany
Stefan Guhlke
- Department of Nuclear Medicine, University of Bonn, Germany
Hans-Jürgen Biersack
- Department of Nuclear Medicine, University of Bonn, Germany
Ullrich Wüllner
- Department of Neurology, University of Bonn, Germany

Received 26 September 2005; received in revised form 5 December 2005; accepted 6 December 2005. published online 13 March 2006.

Abstract

Nicotinic acetylcholine receptors (nAChR) are involved in many physiological functions and appear to be affected in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease (PD). Here, we describe the in vitro evaluation of nAChRs in PD with 2-[¹⁸F]F-A85380, a ligand with high affinity to the β2 nAChR subunit. Autoradiography with 2-[¹⁸F]F-A85380 in untreated rat brain corresponded to the known distribution of α4β2 nAChRs with high uptake in the thalamus, moderate uptake in the striatum and cortex and low uptake in the cerebellum (47%, 43% and 19% of the thalamus, respectively). The localization of α4β2 nAChRs in the striatum was investigated in rodents with unilateral lesion of the substantia nigra. 2-[¹⁸F]F-A85380 binding was significantly reduced in the striatum ipsilateral to the lesion side (to 64% of the contralateral side), indicating that a fraction of α4β2 nAChRs is located on dopaminergic terminals, whereas another fraction resides on striatal interneurons or cortical afferents. Similarly, in human brain sections of PD patients, 2-[¹⁸F]F-A85380 uptake was significantly reduced not only in the caudate and putamen but also in the thalamus (approximately 30% of the binding of control brain in all three regions); within the striatum, nAChRs in the putamen were significantly more severely affected as in the caudate. The observed pattern of α4β2* nAChR loss demonstrates the potential of 2-[¹⁸F]F-A85380 for further investigations of this positron emission tomography ligand for in vivo studies of α4β2* nAChRs in PD.

Keywords: Nicotinic acetylcholine receptor, Fluorine-18, 2-¹⁸F-A85380, Parkinson's disease, PET