Use of 2-[¹⁸F]fluoroethyl bromide in synthesis of O-(2′-[¹⁸F]fluoroethyl)-L-tyrosine, a radiotracer for PET diagnostics of brain tumors

Abstract

The possibility of using 2-[¹⁸F]fluoroethyl bromide ([¹⁸F]FEB) as labeled reagent for selective O-[¹⁸F]fluoroethylation of phenolic group in the presence of an unprotected amino group in an amino acid molecule was demonstrated by the example of the synthesis of O-(2′-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), one of the most promising PET radiotracers for evaluating the rate of transport of amino acids into a tumor tissue. The labeled reagent was prepared by [¹⁸F]fluorination of 2-bromoethyl tosylate with the complex [K/K2.2.2]/[¹⁸F] in o-dichlorobenzene (110°C, 10 min) and was transferred with a nitrogen flow into a solution of the substrate (L-tyrosine, NaOH, dimethyl sulfoxide or dimethyl sulfoxide/o-dichlorobenzene). The reaction with the substrate was performed for 20 min at 100°C; the degree of O-[¹⁸F]fluoroethylation was 75%. [¹⁸F]FET was prepared with a high radiochemical purity (>95%); the total synthesis time, including HPLC purification, was 60 min, and the unoptimized radiochemical yield (corrected for the radioactive decay) was about 20%. The synthesis was performed with an Anatech RB-86 laboratory robot.