Zn2+-Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

The gadolinium(III) complexes GdL1 and GdL2 were designed as Zn2+-responsive bimodal magnetic resonance imaging (MRI) and fluorescence imaging probes. Upon binding to Zn2+ ions, GdL1 exhibits a bidentate or tridentate mode to form heterodinuclear GdL1Zn or heterotrinuclear (GdL1)(2)Zn, whereas GdL2 binds to the Zn2+ ion only in a bidentate mode to form (GdL2)(2)Zn. The gadolinium(III) complexes derived from both H(3)L1 and H(3)L2 exhibit remarkable interactions with human serum albumin (HSA) at both site I and site II, which result in significant enhancements of the relaxivity and remarkable improvements of T-1-weighted imaging contrast. In the presence of HSA, both the relaxivity (r(1)) and fluo-rescence exhibit 300% enhancement with a clear blueshift of the fluorescence for GdL1Zn, which is ascribed to direct binding to HSA through the formation of a Zn-HSA coordination bond. In contrast, the presence of HSA induces smaller relaxivity increases for GdL1 (155%), (GdL1)(2)Zn (183%), GdL2 (192%), and (GdL2) 2Zn (181%); these increases are ascribed to weaker hydrophobic interactions or stereospecificity with HSA. The contrast of T1-weighted phantom MR images of these gadolinium(III) complexes in human serum (HS) is much improved relative to that in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solutions.