title: Environmentally sensitive paramagnetic and diamagnetic contrast agents for nuclear magnetic resonance imaging and spectroscopy.
abstract: Even though alterations in the microenvironmental properties of tissues underlie the development of the most prevalent and morbid pathologies, they are not directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy (MRS) methods. This circumstance has lead to the development of a wide variety of exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non invasively on microenvironmental variables such as pH, pO(2), ion concentration o even temperature. This review covers the fundamentals of environmental contrast and the current arsenal of endogenous and exogenous MRI and MRS contrast enhancing agents available to visualize it. We begin describing the physicochemical background necessary to understand paramagnetic and diamagnetic contrast enhancement with a special reference to novel magnetization transfer and (13)C hyperpolarization strategies. We describe then the main macrocyclic structures used to support the environmentally sensitive paramagnetic sensors, including CEST and PARACEST pH sensitive probes, temperature probes and enzyme activity or gene expression activatable probes. Finally we address the most commonly used diamagnetic contrast agents including imidazolic derivatives to reveal extracellular pH and tissue pO(2) values by MRS. The potential applications of these agents in multimodal and molecular imaging approaches are discussed.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols-CSIC/UAM, c/Arturo Duperier 4, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pacheco-Torres
authors.forename: Daniel
authors.initials: D
authors.lastname: Calle
authors.forename: Blanca
authors.initials: B
authors.lastname: Lizarbe
authors.forename: Viviana
authors.initials: V
authors.lastname: Negri
authors.forename: Carmen
authors.initials: C
authors.lastname: Ubide
authors.forename: Rosa
authors.initials: R
authors.lastname: Fayos
authors.forename: Pilar López
authors.initials: PL
authors.lastname: Larrubia
authors.forename: Paloma
authors.initials: P
authors.lastname: Ballesteros
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cerdan
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000032:analysis*; D004058:Diffusion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010100:Oxygen / Q000737:chemistry
chemical_list: D003287:Contrast Media; D010100:Oxygen