Preparation and first evaluation of [(18)F]FE@SUPPY: a new PET tracer for the adenosine A(3) receptor

Nucl Med Biol. 2008 Jan;35(1):61-6. doi: 10.1016/j.nucmedbio.2007.09.004.

Abstract

Introduction: Changes of the adenosine A(3) 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 [(18)F]FE@SUPPY and a first evaluation of [(18)F]FE@SUPPY in rats.

Methods: [(18)F]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 [(18)F]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.

Conclusion: We conclude that [(18)F]FE@SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Fluorine Radioisotopes*
  • Male
  • Nicotinic Acids / chemical synthesis*
  • Nicotinic Acids / metabolism
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptor, Adenosine A3 / metabolism*
  • Tissue Distribution

Substances

  • 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate
  • Fluorine Radioisotopes
  • Nicotinic Acids
  • Radiopharmaceuticals
  • Receptor, Adenosine A3