Synthesis and characterization of a new bioactivated paramagnetic gadolinium(111) complex [Gd(DOTA-FPG)(H2O)] for tracing gene expression

A smart contrast agent for magnetic resonance imaging (MRI) can be used to exploit an enzymatic activity specific to the tissue or disease state signified by converting an MRI-inactivated agent to an activated MRI agent. In this study, a beta-galactopyranose-containing gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] was designed, synthesized, and characterized as being potentially suitable for a bioactivated MRI contrast agent. The O-17 NMR experiments 29 298 298 were conducted to estimate the water exchange rate k(ex298) and rotational correlation timer(R)(298). The k(ex)(298) value of [Gd(DOTA-FPG)(H2O)] is similar to that of [Gd(DO3A-bz-NO2)(H2O)]. The rotational correlation time value of [Gd(DOTA-FPG)(H2O) is dramatically longer than that of [Gd(DOTA)(H-2O)(-)Relaxometric studies show that the percentage change in the T-1 value of [Gd(DOTA-FPG)(H2O)] decreases dramatically in the presence of beta-galactosidase and human serum albumin. The T-1 change percentage of [Gd(DOTA-FPG)(H2O)] (60%) is significantly higher than those of Egad and gadolinium(III)-1-(4-(2-(1-(4,7,10-triscarboxymethyl-(1,4,7,10-tetraazacyclododecyl)))-ethylcarbamoyloxyniethyl)-2-nitrophenyl)- beta-D-glucopyronuronate. The signal intensity of the MR image for [Gd(DOTA-FPG)(H2O)] in the presence of human serum albumin and beta-galactosidase (2670 +/- 210) is significantly higher than that of [Gd(DOTA-FPG)(H2O)] in the sodium phosphate buffer solution (1490 +/- 160). In addition, the MR images show a higher-intensity enhancement in CT26/beta-gal tumor with beta-galactosidase gene expression but not for the CT26 tumor without beta-galactosidase gene expression. We conclude that [Gd(DOTA-FPG)(H2O)] is a suitable candidate for a bioactivated MRI contrast agent in tracing gene expression.