Selective sensing of zinc ions with a novel magnetic resonance imaging contrast agent†

Abstract

Light-based microscope imaging techniques using fluorescence sensor molecules suffer from photobleaching and light scattering, but magnetic resonance imaging (MRI) can provide three-dimensional imaging without these problems. Recently, “smart” MRI contrast agents which modulate the access of water to a chelated gadolinium (Gd3+) ion in the presence or absence of a specific trigger have been reported. Zinc (Zn2+) is an essential component of many enzymes, transcription factors and synaptic vesicles in excitatory nerve terminals, so imaging of chelatable Zn2+ is of interest. We have designed and synthesized the Gd3+ DTPA bisamide complex 7a as a Zn2+-sensitive MRI contrast agent. Compound 7a shows a dose-dependent change in the R1 relaxivity in the presence of Zn2+. We investigated this relaxation behavior, and for this purpose we also synthesized the Gd3+ DTPA amide ethyl ester complex 7b. It was shown that binding between 7a and Zn2+ caused a change in the relaxation time. Moreover, 7a had high selectivity for Zn2+ against Ca2+ and Mg2+. Compound 7a may have practical problems for in vivo usage, since the R1 relaxivity is reduced with increased Zn2+ concentration. However, this report demonstrates new approaches to the design and synthesis of Gd3+ complexes with R1 values that change with variation in Zn2+ concentration.