18F-labeled tyrosine derivatives: Synthesis and experimental studies on accumulation in tumors and abscesses

Tyrosine derivatives labeled with a short-lived fluorine-18 isotope (T1/2 110 min), namely 2-[18F]fluoro-L-tyrosine (FTYR) and O-(2′-[18F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceuticals (RPs) for positron emission tomography (PET), were obtained by asymmetric syntheses. Accumulation of FTYR and FET in the rat tumor “Glioma 35 rats tumor” and in abscesses induced in Wistar rats muscles was studied and compared with that of a well-known glycolysis radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (FDG). It was shown that the relative accumulation indices of amino acid RPs were considerably lower than those of FDG. At the same time, tumor/muscle ratios were high enough (2.9 for FET and 3.9 for FTYR 120 min after injection) for reliable tumor visualization. The data obtained indicated a possibility in principle to use FTYR and FET for differentiated PET diagnostics of brain tumors and inflammation lesions. Of the tyrosine derivatives studied, FET seems to be the most promising agent due to a simple and easily automated method of preparation based on direct nucleophilic substitution of the leaving tosyloxy group of an enantiomerically pure Ni-(S)-BPS-(S)-Tyr(CH2CH2OTs) precursor by an activated [18F]fluoride.