A novel class of 1H-MRI Contrast Agents based on the relaxation enhancement induced on water protons by 14N imidazole moieties

This study aims at developing a completely new class of MRI contrast agents, displaying remarkable relaxation effects in the absence of paramagnetic metal ions. Their detection requires the acquisition of images at variable magnetic field strength as provided by Fast Field Cycling imaging scanners. They contain poly-histidine chains (poly-His), whose imidazole groups generate 14N-QuadrupolarPeaks that cause a relaxation enhancement of water protons at a frequency (1.38±0.3 MHz) that is readily detectable from the frequencies associated with endogenous proteins. The poly-His QPs are detectable only when the polymer is in a solid-like form, i.e. at pH > 6.6. Above this value, their intensity is pH dependent and can beused to report on the occurring pH changes. On this basis, the polyHis moieties were conjugated to biocompatible polymers such aspolylactic and glycolic acid, in order to form stable nanoparticles ableto encapsulate structured water in their core. FFC images were acquired to assess their contrast-generating ability.