Redox Properties and in Vivo Magnetic Resonance Imaging of Cyclodextrin-Polynitroxides Contrast Agents

This paper reports the synthesis, characterization and in vivo application of water-soluble supramolecular contrast agents (Mw: 5–5.6 kDa) for MRI obtained from β-cyclodextrin functionalized with different kinds of nitroxide radicals, both with piperidine structure ( CD2 and CD3 ) and with pyrrolidine structure ( CD4 and CD5 ). As to the stability of the radicals in presence of ascorbic acid, CD4 and CD5 have low second order kinetic constants (≤0.05 M^?1 s^?1) compared to CD2 (3.5 M^?1 s^?1) and CD3 (0.73 M^?1 s^?1). Relaxivity (r₁) measurements on compounds CD3 - CD5 were carried out at different magnetic field strength (0.7, 3, 7 and 9.4 T). At 0.7 T, r₁ values comprised between 1.5 mM^?1 s^?1 and 1.9 mM^?1 s^?1 were found while a significant reduction was observed at higher fields (r₁≈0.6-0.9 mM^?1 s^?1 at 9.4 T). Tests in vitro on HEK293 human embryonic kidney cells, L929 mouse fibroblasts and U87 glioblastoma cells indicated that all compounds were non-cytotoxic at concentrations below 1 μmol mL^?1. MRI in vivo was carried out at 9.4 T on glioma-bearing rats using the compounds CD3 - CD5 . The experiments showed a good lowering of T₁ relaxation in tumor with a retention of the contrast for at least 60 mins confirming improved stability also in vivo conditions.