Lanthanide(III) Complexes of Diethylenetriaminepentaacetic Acid (DTPA)-Bisamide Derivatives as Potential Agents for Bimodal (Optical/Magnetic Resonance) Imaging

Diethylenetriaminepentaacetic acid (DTPA)bisamide derivatives functionalized with p-toluidine, 6-aminocoumarin, 1-naphthalene methylamine and 4-ethynylaniline were synthesized and fully characterized by mass spectrometry, NMR spectroscopy, FTIR spectroscopy and elemental analysis. LnIII complexes (Ln = Gd, Eu, Tb, Y) of the ligands DTPAbis-p-toluidineamide (DTPABTolA), DTPAbis-6-coumarinamide (DTPABCoumA), DTPAbis-1-naphthylmethylamide (DTPABNaphA) and DTPAbis-4-ethynylphenylamide (DTPABEthA) were prepared and studied for their bimodal magnetic resonance imaging/optical properties. EuIII and TbIII derivatives in aqueous solutions exhibit characteristic red and green emission, respectively, with quantum yields of 0.73% for EuIIIDTPABNaphA and 2.5% for TbIIIDTPABEthA. Ligand-centred photophysical properties of the GdIII complexes were investigated to gain insight into energy-transfer processes that take place in these systems. The GdIII complexes were also analyzed by nuclear magnetic relaxation dispersion (NMRD) techniques. The relaxivity (r1) at 20 MHz and 310 K equals 4.1 s1mM1 for GdDTPABTolA, 5.1 s1mM1 for GdDTPABCoumA, 6.4 s1mM1 for GdDTPABNaphA and 5.7 s1mM1 for GdDTPABEthA. These values are higher than the value of 3.8 s1mM1 for GdDTPA (Magnevist). The improved relaxivity is due to the increase in the rotational tumbling time R with a factor of 1.6 for GdDTPABTolA, 2.1 for GdDTPABCoumA, 3.1 for GdDTPABNaphA and 6.5 for GdDTPABEthA. In a 4% human serum albumin solution, the apparent relaxivity at 20 MHz increases to values of 13.9 and 19.1 s1mM1 for GdDTPABNaphA and GdDTPABEthA, respectively. All these features assist the search for optimal bimodal optical and magnetic resonance imaging probes.