Preparation and first evaluation of [18F]FE@SUPPY: a new PET tracer for the adenosine A3 receptor

Wadsak, Wolfgang; Mien, Leonhard-Key; Shanab, Karem; Ettlinger, Dagmar E.; Haeusler, Daniela; Sindelar, Karoline; Lanzenberger, Rupert R.; Spreitzer, Helmut; Viernstein, Helmut; Keppler, Bernhard K.; Dudczak, Robert; Kletter, Kurt; Mitterhauser, Markus

doi:10.1016/j.nucmedbio.2007.09.004

« Previous Next »Nuclear Medicine and Biology
Volume 35, Issue 1 , Pages 61-66, January 2008

Preparation and first evaluation of [¹⁸F]FE@SUPPY: a new PET tracer for the adenosine A₃ receptor

Wolfgang Wadsak
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
- Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna, Austria
Leonhard-Key Mien
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria
Karem Shanab
- Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
Dagmar E. Ettlinger
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
Daniela Haeusler
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria
Karoline Sindelar
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
Rupert R. Lanzenberger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria
Helmut Spreitzer
- Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
Helmut Viernstein
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria
Bernhard K. Keppler
- Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna, Austria
Robert Dudczak
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
Kurt Kletter
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
Markus Mitterhauser
- Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria
- Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna, Austria
- Corresponding author. Department of Nuclear Medicine, AKH Wien, Waehringer Guertel 18–20, A-1090 Vienna, Austria. Tel.: +43 1 40400 1557; fax: +43 1 40400 1559.

Received 13 August 2007; received in revised form 11 September 2007; accepted 27 September 2007.

Abstract

Introduction

Changes of the adenosine A₃ receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [¹⁸F]FE@SUPPY and a first evaluation of [¹⁸F]FE@SUPPY in rats.

Methods

[¹⁸F]FE@SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA.

Results

Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [¹⁸F]FE@SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist.