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

Abstract

AbstractDiethylenetriaminepentaacetic 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 DTPA–bis‐p‐toluidineamide (DTPA–BTolA), DTPA–bis‐6‐coumarinamide (DTPA–BCoumA), DTPA–bis‐1‐naphthylmethylamide (DTPA–BNaphA) and DTPA–bis‐4‐ethynylphenylamide (DTPA–BEthA) 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 EuIII–DTPA–BNaphA and 2.5 % for TbIII–DTPA–BEthA. 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 s–1 mM–1 for Gd–DTPA–BTolA, 5.1 s–1 mM–1 for Gd–DTPA–BCoumA, 6.4 s–1 mM–1 for Gd–DTPA–BNaphA and 5.7 s–1 mM–1 for Gd–DTPA–BEthA. These values are higher than the value of 3.8 s–1 mM–1 for Gd–DTPA (Magnevist). The improved relaxivity is due to the increase in the rotational tumbling time τR with a factor of 1.6 for Gd–DTPA–BTolA, 2.1 for Gd–DTPA–BCoumA, 3.1 for Gd–DTPA–BNaphA and 6.5 for Gd–DTPA–BEthA. In a 4 % human serum albumin solution, the apparent relaxivity at 20 MHz increases to values of 13.9 and 19.1 s–1 mM–1 for Gd–DTPA–BNaphA and Gd–DTPA–BEthA, respectively. All these features assist the search for optimal bimodal optical and magnetic resonance imaging probes.