Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

Magnetic resonance imaging examinations are frequently carried out using contrast agents to improve the image quality. Practically all clinically used contrast agents are based on paramagnetic metals and lack in selectivity and specificity. A group of stable organic radicals, nitroxides, has raised interest as new metal-free contrast agents for MRI. Their structures can easily be modified to incorporate different functionalities. In the present study, a stable nitroxide TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl) was linked to a glucose moiety (Glc) to construct a water-soluble, potentially tumor-targeting compound with contrast-enhancing ability. The ability was assessed with in vivo MRI experiments. The constructed TEEPO-Glc agent proved to shorten the T-1 relaxation time in tumor, while the T-1 time in healthy brain tissue remained the same. The results indicate the potential of TEEPO-Glc as a valuable addition to the growing field of metal-free contrast enhancement in MRI-based diagnostics.Peer reviewe

Cyclodextrin‐Based Organic Radical Contrast Agents for In Vivo Imaging of Gliomas

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 defining the role of the CD macrocycle on the effective magnetic moment (μeff). It increased from 3.982 μB(CD61) to 4.522 μB (CD81) but was limited by intra-molecular 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 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