Calix[4]arenes as Molecular Platforms in Magnetic Resonance Imaging

Abstract

Magnetic resonance imaging (MRI) is an important tool in medical diagnosis. It uses non-ionizing radio-frequency radiation and produces images with excellent resolution. To increase the contrast, Gd(III)-containing compounds are applied leading to a brightening of the area of interest. The performance of a contrast agent can be enhanced by using large and at the same time rigid systems to bind the paramagnetic Gd(III). Since calix[4]arenes can be rigidified and functionalized easily, they were chosen as molecular building blocks to attach Gd(III)-containing units to them. Those conjugates were optimized to yield highly efficient MRI contrast agents that self-assemble in water to nano-sized aggregates. Their interaction with the plasma protein human serum albumin gives them the potential to be used in angiography. To extend their application even further, nano-vesicles (liposomes) were prepared that contain such a conjugate in their walls. Thanks to the presence of the calix[4]arene core, those liposomes have unprecedentedly high contrast enhancement properties. Due to this and the fact that liposomes are known to accumulate in tumours, this probe is a promising candidate for cancer imaging. The broad applicability of the calix[4]arene core in medical sciences is further demonstrated in investigations towards sodium-selective artificial ion channels as well as towards a deeper understanding of the functioning of model compounds that mimic the hydrophobic active pocket of enzymes.