The Open Nuclear Medicine Journal

2009, 1 : 15-23
Published online 2009 May 20. DOI: 10.2174/1876388X00901010015
Publisher ID: TONMEDJ-1-15

Automatisation and First Evaluation of [F]FE@SUPPY:2, an Alternative PET-Tracer for the Adenosine A Receptor: A Comparison with [F]FE@SUPPY

Markus Mitterhauser , Daniela Haeusler , Leonhard-Key Mien , Johanna Ungersboeck , Lukas Nics , Rupert R Lanzenberger , Karoline Sindelar , Helmut Viernstein , Robert Dudczak , Kurt Kletter , Helmut Spreitzer and Wolfgang Wadsak
Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria.

ABSTRACT

Introduction:

Since the Adenosine-A3-receptor was identified in the late 1990´s, there is little data available describing its distribution in vivo. Recently, we introduced [18F]FE@SUPPY as the first PET-tracer for this receptor. In the present investigation we translated this fluoroethyl-ester into the fluoroethyl-thioester [18F]FE@SUPPY:2 (5-ethyl 2,4- diethyl-3-((2-[18F]fluoroethyl) sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate). Aims of the present study were the evaluation of (1) the automatized preparation of both [18F]FE@SUPPY-derivatives, (2) the biodistribution of [18F]FE@SUPPY:2, (3) the lipophilicity and (4) the comparison of the findings of [18F]FE@SUPPY and [18F]FE@SUPPY:.

Methods:

The automated preparations of both [18F]FE@SUPPY-analogs were performed on a GE TRACERlab FxFN synthesizer using suitable precursors. Biodistribution experiments were performed using Sprague-Dawley rats/Him:OFA. Lipophilicity of the compounds was determined using an HPLC assay.

Results:

22 automated radiosyntheses were performed for both radiotracers. Specific radioactivity was 70 ± 26GBq/µmol for [18F]FE@SUPPY and 340 ± 140GBq/µmol for [18F]FE@SUPPY:2. Biodistribution experiments evinced bowels and liver as organs with highest uptake and intermediate uptake in kidney, lung and heart. LogP values of both molecules ranged from 3.99 to 4.12 at different pH.

Conclusion:

From a radiopharmaceutical perspective, drastically better specific radioactivities would militate in favour of [18F]FE@SUPPY:2; preclinical evaluations, so far, do not permit the decision upon the selection of the optimum [18F]FE@SUPPY-derivative. With [18F]FE@SUPPY:2, we are able to provide a second potential tracer that could help to further characterize the still quite unexplored Adenosine-A3-receptor.

Keywords:

Adenosine, PET, adenosine A3 receptor.