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

Cyclodextrins (CDs), a class of cyclic oligosaccharides formed by alpha-(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 thein vivodetection 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 (mu(eff)). The mu(eff)value increased from 3.982 mu(B)(CD61) to 4.522 mu(B)(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(1)H water relaxivities r(1)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 relaxivityin vivo.