Synthesis and in vitro phantom NMR and MRI studies of fully organic free radicals, TEEPO-glucose and TEMPO-glucose, potential contrast agents for MRI

Abstract

Two organic radical contrast agents, TEMPO-Glc and TEEPO-Glc, were synthesized and their stabilities and contrast enhancing properties were tested with in vitro NMR and MRI experiments. Owing to the glucose moieties in the prepared compounds, this study presents potential candidates for a tumor targeting fully organic contrast agents for MRI.

Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

“…The plots of the 1 H relaxation rate of water (1/T 1 ) versus the nitroxide concentration were linear for all agents, indicating the absence of aggregation ( Figure S7.1). The per-nitroxide r 1 values ranged from 0.33 to 0.51 mM −1 s −1 (Table 4), making them comparable to those reported in various nitroxide-bound polymers and dendrimers [15,29] and higher than for potential low-molecular-weight, nitroxide-based MRI probes at 7 T [20,21]. Moreover, per-nitroxide r 2 values ranged from 4.7 to 7.2 mM −1 s −1 , much greater than what is typical for individual nitroxides in solution; e.g., 2 has r 1 and r 2 of 0.15 and 0.17 mM −1 s −1 , respectively [76].…”

“…Bio-oxidation is rare and not a problem [28,75]. We evaluated the reduction rates of nitroxide groups in the conjugates and in 1-4 by ascorbate, the reducing agent standardly used to estimate the redox properties of nitroxides [21,29,54]. Reduction rates were measured under pseudo-first-order R=OH 0.063 [26,29] 0.097 [ The EPR spectra from nitroxides at each modification site overlap, preventing characterization of individual modification sites by EPR.…”

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

“…However, nitroxides with bulky side groups have shown remarkable stability in conditions mimicking biological matrix [23,24]. e research of nitroxide-based contrast agents comprises both macromolecular [25][26][27][28][29][30][31] and small molecule [32][33][34][35][36] systems. It is often considered that the advantage of using polymers or nanomaterials as a backbone for nitroxides is the possibility to attach several radical centers to the contrast agent molecule.…”

“…Our study has focused on attaching a highly stable nitroxide, TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl), to natural compound moieties that can potentially act as targeting units [35,36]. e method is commonly applied in the use of radiopharmaceuticals as tracers in PET (positron emission tomography) imaging [37].…”

“…e method is commonly applied in the use of radiopharmaceuticals as tracers in PET (positron emission tomography) imaging [37]. In our rst study, we presented the synthesis of TEEPO-Glc (Figure 1), where TEEPO is covalently attached to a glucose molecule [35]. One of the main advances of using glucose is its ability to increase the water solubility of the otherwise lipophilic TEEPO.…”