RESUMO
Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an unpaired electron to chemical reduction with low-molecular-weight antioxidants and enzymatic systems is of critical importance for these applications. The redox properties of nitroxides are known to depend on the ring size (for cyclic nitroxides) and electronic and steric effects of the substituents. Here, two highly strained nitroxides, 5-(tert-butyl)-5-butyl-2,2-diethyl-3-hydroxypyrrolidin-1-oxyl (4) and 2-(tert-butyl)-2-butyl-5,5-diethyl-3,4-bis(hydroxymethyl)pyrrolidin-1-oxyl (5), were prepared via a reaction of the corresponding 2-tert-butyl-1-pyrroline 1-oxides with butyllithium. Thermal stability and kinetics of reduction of the new nitroxides by ascorbic acid were studied. Nitroxide 5 showed the highest resistance to reduction.
Assuntos
Antioxidantes/química , Óxidos de Nitrogênio/química , Compostos Organometálicos/química , Pirróis/química , Antioxidantes/síntese química , Pesquisa Biomédica/tendências , Transporte de Elétrons , Compostos Organometálicos/síntese química , Oxirredução , Óxidos/química , Pirróis/síntese químicaRESUMO
Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content.
Assuntos
Acidose/diagnóstico , Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética , Fosfatos/isolamento & purificação , Acidose/diagnóstico por imagem , Acidose/metabolismo , Acidose/patologia , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Meios de Contraste/farmacologia , Modelos Animais de Doenças , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Fosfatos/metabolismo , Hipóxia Tumoral/efeitos dos fármacosRESUMO
Overhauser-enhanced Magnetic Resonance Imaging (OMRI) is a double resonance technique applied for oxygen imaging in aqueous samples and biological tissues. In this report, we present an improved OMRI approach of oxygen measurement using the single line "Finland" trityl spin probe. Compared to a traditional approach, we introduced an additional mechanism of leakage of spin polarization due to an interaction of a spin system with oxygen. The experimental comparison of the new approach with an oxygen-dependent leakage factor to a traditional approach performed in phantom samples in vitro, and mouse tumor model in vivo, shows improved accuracy of determination of oxygen and contrast agent concentrations.