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

Abstract

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.

2,5-Di-tert-butyl-2,5-diethylpyrrolidine-1-oxyls: Where Is a Reasonable Limit of Sterical Loading for Higher Resistance to Reduction?

“…Nitroxides are a broad family of organic free radicals which have been of constantly growing interest to researchers for many decades [1][2][3]. The relative simplicity of chemical modification of nitroxide structures resulted in the synthesis of countless numbers of derivatives, allowing for tuning of their chemical and physical properties and spectral parameters for specific applications in various fields of science and technology [4][5][6][7][8][9][10][11][12]. Rapid development of the chemistry of nitroxides is facilitating the progress in their applications.…”