2-2-5-5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic-acid and nitroxyl

In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd. Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM. As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs.

Topics: Animals; Cell Survival; Contrast Media; Cyclic N-Oxides; Female; Gadolinium; Heart; Kidney; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Nitrogen Oxides; Polymers

Clearance of the nitroxide radicals, hydroxy-TEMPO and carboxy-PROXYL, in whole-mouse lung was directly measured by in vivo ESR. After injecting a nitroxide radical, distribution of the nitroxide radical all over the lung was confirmed by ESR imaging. The ESR signal of hydroxy-TEMPO was reduced in the lung and the clearance obeyed first-order kinetics, whereas the signal of carboxy-PROXYL remained constant. Comparison of the clearance rates of live and dead mice indicated the presence of 2 different clearance systems in the lung: loss of its paramagnetism in the lung, and transfer from alveolar to the blood circulation system.

Topics: Animals; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Lung; Metabolic Clearance Rate; Mice; Muscles; Nitrogen Oxides; Spin Labels

The in vivo uptake distribution and reduction of the oxygen-sensitive nitroxide spin label PCA in the mouse monitored by low frequency electron paramagnetic resonance (EPR) spectroscopy are reported. Spectra were obtained from the head and liver regions of pentobarbital anesthetized mice during different circulatory and ventilatory conditions. Identical clearances were found in these regions during normoxia. Moderate hypoxia (10% O2-90% N2) did not significantly affect the spin label reduction rate.

Topics: Animals; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Free Radicals; Head; Metabolic Clearance Rate; Mice; Nitrogen Oxides; Spin Labels