Uridine-based paramagnetic supramolecular nanoaggregate with high relaxivity capable of detecting primitive liver tumor lesions

The water soluble uridine-based paramagnetic self-assembled amphiphilic molecules (LGd2-5) with DTTA binding site were synthesized and have been characterized in regard to their T₁ magnetic resonance imaging (MRI) contrast agent (CA) properties. The water proton relaxivities have been measured in phosphate buffered saline (PBS) at 36 °C at 3 different magnetic fields. Among the self-assembled CAs, LGd3 showed unprecedented, high relaxivities of 30.3 and 23.4 mM^-1 s^-1 in PBS solution at 36 °C at 0.47 and 1.41 T, respectively. The non-covalent interactions between the new CAs and human serum albumin (HSA) have been investigated and the relaxivity was further increased by 135-215% depending on alkyl chain lengths. The chemically inertness of these complexes (LGd1, LGd2, LGd3, LGd4) against biologically most abundant metal ion (i.e. Zn²⁺) have shown within the range of commercial DTPA-based CAs. In vivo pharmacokinetics of the complex LGd3 showed highly specific for hepatocytes resulting in increase of contrast noise ratio by ∼240% in T₁-weighted MR images of mouse liver 2 h after injection of the LGd3. It is capable to detect small hepatocellular carcinoma (HCC) with diameter of 1.5 mm.