[(18)F-labeled tyrosine derivatives: synthesis and experimental studies on accumulation in tumors and abscesses].
Tyrosine derivatives labeled with a short-living fluorine 18 isotope (T(1/2) 110 min), namely 2-[(18)F]fluoro-L-tyrosine (FTYR) and O-(2'-[(18)F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceutical products (RPP) for positron emission tomography (PET), were obtained by asymmetric synthesis. Accumulation of FTYR and FET in the rat tumor "35 rat glioma" and in abscesses induced in Vistar mouse muscles was studied and compared with that of a well-known glycolysis radiotracer 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG). It was shown that the relative accumulation indices of amino acid RPP 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)-BPB-(S)-Tyr(CH2CH2OTs) precursor by an activated [(18)F]fluoride.
Fedorova
O S
OS
Institute of the Human Brain, Russian Academy of Sciences, ul. Akademika Pavlova 9, St. Petersburg, 197376 Russia.
Kuznetsova
O F
OF
Shatik
S V
SV
Stepanova
M A
MA
Belokon'
Iu N
IuN
Maleev
V I
VI
Krasikova
R N
RN
D000038:Abscess / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D007553:Isotope Labeling; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine; C060489:2-fluorotyrosine