Synthesis of radioiodine-labeled 2-phenylethyl 1-thio-β-D-galactopyranoside for imaging of LacZ gene expression

A potent inhibitor of β-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-β-D-galactopyranoside (PETG), was radioiodinated for noninvasive imaging of LacZ gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2-(4-bromophenyl)ethanethiol was prepared and attached to the C-1 position of β-D-galactose pentaacetate under conditions that resulted in the exclusive formation of the β anomer. The bromo group of PETG was converted to the tributylstannyl group where radioiododemetallation was carried out. Radioiodine-labeled PETG tetraacetate was purified by HPLC, which can be used as a prodrug for biological evaluation or hydrolyzed to 2-(4-[¹²³I/¹²⁵I]iodophenyl)ethyl 1-thio-β-D-galactopyranoside ([¹²³I/¹²⁵I]7) under basic conditions. The resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical yield (decay-corrected) and with specific activity of 46-74 GBq/μmol.