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

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 R₁relaxivity 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 R₁relaxivity is reduced with increased Zn²⁺concentration. However, this report demonstrates new approaches to the design and synthesis of Gd³⁺complexes with R₁values that change with variation in Zn²⁺concentration.