A new ditopic Gd^III complex functionalized with an adamantyl moiety as a versatile building block for the preparation of supramolecular assemblies Topical Issue on Metal-Based MRI Contrast Agents. Guest editor: Valerie C. Pierre

A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4- diazepinetetraacetic acid) bearing an adamantyl group (Gd₂ L1) able to form strong supramolecular adducts with specific hosts such as β-cyclodextrin (β-CD), poly-β-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd₂ L1 were investigated in aqueous solution by measuring the ¹H relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd₂ L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM^-1 s^-1, a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5-3.0 T). The noncovalent interaction of Gd₂ L1 with β-CD, poly-β-CD, and HSA and the relaxometric properties of the resulting host-guest adducts were investigated using ¹H relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd₂ L1-β-CD and Gd₂ L1-poly-β-CD, respectively. Binding of Gd₂ L1 to HSA (K _A = 1.2 × 10⁴ M ^-1) results in a remarkable relaxivity of 41.4 mM^-1 s ^-1 for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd₂ L1-β-CD to Gd₂ L1-HSA. Finally, the applicability of Gd₂ L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation.