Papers - Hanaoka, Kenjiro

Design and synthesis of a novel magnetic resonance imaging contrast agent for selective sensing of zinc ion

Hanaoka K., Kikuchi K., Urano Y., Narazaki M., Yokawa T., Sakamoto S., Yamaguchi K., Nagano T.

Chemistry and Biology (Chemistry and Biology)  9 ( 9 ) 1027 - 1032 2002.09

Research paper (scientific journal), Accepted,  ISSN  10745521

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A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as zinc sensors. We have designed and synthesized (GdLa)2-, which contains a DTPA-bisamide moiety. The R1 relaxivity of (GdLa)2- solution decreased monotonically on the addition of Zn2+. Moreover, (GdLa)2- showed high selectivity for Zn2+ against Ca2+ and Mg2+. We also measured the UV-visible spectra and the coldspray ionization (CSI) MS spectra and concluded that the 1-to-1 Zn2+ complex of (GdLa)2- is stable at higher concentrations of Zn2+. These complexes should provide the basis for creating a superior Zn2+-sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn2+ in biological applications.

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

Hanaoka K., Kikuchi K., Urano Y., Nagano T.

Journal of the Chemical Society. Perkin Transactions 2 (Journal of the Chemical Society. Perkin Transactions 2)  1 ( 9 ) 1840 - 1843 2001

Research paper (scientific journal), Accepted,  ISSN  03009580

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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. © 2001 The Royal Society of Chemistry.

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