Redox properties and in vivo magnetic resonance imaging of cyclodextrin-polynitroxides contrast agents

• Published in: Chemphyschem Vol. 24; no. 19; p. e202300100
• Main Authors: Franco, Lorenzo, Isse, Abdirisak Ahmed, Barbon, Antonio, Altomare, Lina, Hyppönen, Viivi, Rosa, Jessica, Olsson, Venla, Kettunen, Mikko, Melone, Lucio
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04.10.2023
• Subjects: Ascorbic acid; Contrast agents; Cyclodextrins; Fibroblasts; Field strength; Glioma; In vivo methods and tests; Magnetic properties; Magnetic resonance imaging; Piperidine; glioma; MRI imaging; contrast agents; nitroxides; cyclodextrin
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.202300100

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 (≤0.06 M-1 s-1) compared to CD2 (3.5 M-1 s-1) and CD3 (0.73 M-1s-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-1s-1 and 1.9 mM-1s-1 were found while a significant reduction was observed at higher fields (r1≈0.6-0.8 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 and 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.