Synthesis and preliminary evaluation of (R,R)(S,S) 5-(2-(2-[4-(2-[(18)F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([(18)F]FEFE) for the in vivo visualisation and quantification of the beta2-adrenergic receptor status in lung.
The (18)F-labeled beta2-adrenergic receptor ligand (R,R)(S,S) 5-(2-(2-[4-(2-[(18)F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol, a derivative of the original highly selective racemic fenoterol, was synthesized in an overall radiochemical yield of 20% after 65 min with a radiochemical purity higher than 98%. The specific activity was in the range of 50-60 GBq/micromol. In vitro testing of the non-radioactive fluorinated fenoterol derivative with isolated guinea pig trachea was conducted to obtain an IC(50) value of 60 nM. Preliminary ex vivo organ distribution and in vivo experiments with positron emission tomography (PET) on guinea pigs were performed to study the biodistribution as well as the displacement of the radiotracer to prove specific binding to the beta2-receptor.
Schirrmacher
Esther
E
Institute of Nuclear Chemistry, University of Mainz, Fritz Strassmann-Weg 2, D-55128, Mainz, Germany. frank.roesch@uni-mainz.de
Schirrmacher
Ralf
R
Thews
Oliver
O
Dillenburg
Wolfgang
W
Helisch
Andreas
A
Wessler
Ignatz
I
Buhl
Roland
R
Höhnemann
Sabine
S
Buchholz
Hans Georg
HG
Bartenstein
Peter
P
Machulla
Hans Jürgen
HJ
Rösch
Frank
F
D000818:Animals; D005280:Fenoterol / Q000031:analogs & derivatives* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D066298:In Vitro Techniques; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D008956:Models, Chemical; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D018343:Receptors, Adrenergic, beta-2; D005280:Fenoterol