Cyclodextrin‐Based Organic Radical Contrast Agents for in vivo Imaging of Gliomas

• Published in: ChemPlusChem (Weinheim, Germany) Vol. 85; no. 6; pp. 1171 - 1178
• Main Authors: Melone, Lucio, Bach, Alice, Lamura, Gianrico, Canepa, Fabio, Nivajärvi, Riikka, Olsson, Venla, Kettunen, Mikko
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2020
• Subjects: Animals; contrast agents; Contrast Media - chemistry; Cyclic N-Oxides - chemistry; cyclodextrins; Cyclodextrins - chemistry; Female; Glioma - diagnostic imaging; gliomas; Magnetic Resonance Imaging; polynitroxides; Rats, Wistar; polynitroxides; magnetic resonance imaging; gliomas; cyclodextrins; contrast agents
• ISSN: 2192-6506; 2192-6506
• DOI: 10.1002/cplu.202000190

Cyclodextrins (CDs), a class of cyclic oligosaccharides formed by α‐(1,4) linked glucopyranose units, were functionalized with (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) radicals to prepare water soluble supramolecular organic radical contrast agents (ORCAs) for the in vivo detection of glioma tumor in animal models. A first set of molecules (CDn1, n=6,7,8 is the number of both TEMPO and glucopyranose units) was studied by superconducting quantum interference devices (SQUID) magnetometry in order to define the role of the CD macrocycle on the effective magnetic moment (μeff). The μeff value increased from 3.982 μB(CD61) to 4.522 μB (CD81) but was limited by intramolecular antiferromagnetic (AF) interactions. A set of water‐soluble ORCAs (CDn8, n=6,7,8) was prepared by a sequence of thiol‐ene and Cu(I)‐catalyzed alkyne–azide “click” reactions. Their 1H water relaxivities r1 of these ORCAs were between 0.739 mM−1 s−1 (CD68) to 1.047 mM−1 s−1 (CD88) in D2O/H2O 9 : 1 (v : v) at 300 K. One of them (CD78) was tested on glioma‐bearing rats with reduced side effects and good relaxivity in vivo. Soluble in water: A family of cyclodextrin‐based water‐soluble organic radical contrast agents was synthesized by a straightforward combination of thiol‐ene and Cu(I)‐catalyzed alkyne‐azide “click” reactions. Their 1H water relaxivities r1 were between 0.739 mM−1 s−1 to 1.047 mM−1 s−1 in D2O/H2O 9 : 1 (v : v) at 300 K. Aqueous solutions with concentration up to 200 mM were easily prepared. These compounds were investigated as contrast agents for the in vivo detection of glioma tumor in animal models.