title: [18F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents.
abstract: OBJECTIVE
  The adenosine A3 receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY.
  
  
  METHODS
  Rats were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated.
  
  
  RESULTS
  [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [(18)F]FE@SUPPY was stable in human plasma.
  
  
  CONCLUSIONS
  Selective and significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [(18)F]FE@SUPPY in "humanized animal models". In conclusion, preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET tracer in humans.
authors.affiliation: Department of Nuclear Medicine, Medical University of Vienna, 1090, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuntner
authors.forename: Lukas
authors.initials: L
authors.lastname: Nics
authors.forename: Markus
authors.initials: M
authors.lastname: Savli
authors.forename: Markus
authors.initials: M
authors.lastname: Zeilinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Wanek
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.forename: Rupert R
authors.initials: RR
authors.lastname: Lanzenberger
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.forename: Karem
authors.initials: K
authors.lastname: Shanab
authors.forename: Helmut
authors.initials: H
authors.lastname: Spreitzer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C528136:5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate; D009539:Nicotinic Acids; D019275:Radiopharmaceuticals; D043684:Receptor, Adenosine A3