서강대학교

초록/요약

Positron emission tomography has received a great attention as a clinically applicable molecular imaging tool. Of various positron emitters, F-18 is the most attractive on the basis of proper physical and chemical properties. Unlike small synthetic molecules, [18F]radiofluorination of biomolecule-based disease targeting substances needs a special and careful treatment during synthesis and purification. With this regard, two 18F-labeled prosthetic groups, i.e., succinimidyl ester and maleimide have been developed using mild copper(I)-catalyzed azide/alkyne [3+2]cycloaddition (CuAAC). While previous methods comprise multi-step synthesis and long preparation time, click method offered not only short synthetic steps and time, but also high radiochemical yield (RCY) and purity (RCP). Our method consists of two steps, [18F]fluorination and click ligation. [18F]Fluorination of azide precursor was completed within 10 min under heating at 120 oC with good RCY. After simple silica filtration, the resulting filtrate was reacted with compound 5 and N-propargyl maleimide or N-(4-pentynyl) maleimide or N-{2-[2-(2-propargyloxy)ethoxy]ethoxy}ethyl maleimide in the presence of CuI and Et3N to give the corresponding 1,2,3-triazole-linked 18F-labeled maleimide in excellent yields. They were then purified by HPLC within 20 min, and used in ligation of glutathione peptide by terms of Michael addition-type reaction between 18F-labeled maleimide and sulfide of glutathione.