Chemical exchange saturation transfer contrast agents for magnetic resonance imaging.

Magnetic resonance imaging (MRI) contrast agents have become an important tool in clinical medicine. The most common agents are Gd(3+)-based complexes that shorten bulk water T(1) by rapid exchange of a single inner-sphere water molecule with bulk solvent water. Current gadolinium agents lack tissue specificity and typically do not respond to their chemical environment. Recently, it has been demonstrated that MR contrast may be altered by an entirely different mechanism based on chemical exchange saturation transfer (CEST). CEST contrast can originate from exchange of endogenous amide or hydroxyl protons or from exchangeable sites on exogenous CEST agents. This has opened the door for the discovery of new classes of responsive agents ranging from MR gene reporter molecules to small molecules that sense their tissue environment and respond to biological events.

[1]  J. Klaveness,et al.  Gadolinium DO3A derivatives mimicking phospholipids; preparation and in vitro evaluation as pH responsive MRI contrast agents , 2001 .

[2]  Y. Urano,et al.  Selective sensing of zinc ions with a novel magnetic resonance imaging contrast agent , 2001 .

[3]  L. Helm,et al.  Structural and Dynamic Parameters Obtained from 17O NMR, EPR, and NMRD Studies of Monomeric and Dimeric Gd3+ Complexes of Interest in Magnetic Resonance Imaging: An Integrated and Theoretically Self-Consistent Approach1 , 1996 .

[4]  Piotr Walczak,et al.  Artificial reporter gene providing MRI contrast based on proton exchange , 2007, Nature Biotechnology.

[5]  Enzo Terreno,et al.  Highly sensitive MRI chemical exchange saturation transfer agents using liposomes. , 2005, Angewandte Chemie.

[6]  E. W. Meijer,et al.  Dendritic PARACEST contrast agents for magnetic resonance imaging. , 2007, Contrast media & molecular imaging.

[7]  M. Botta,et al.  Gd(III) complexes as contrast agents for magnetic resonance imaging: a proton relaxation enhancement study of the interaction with human serum albumin , 1996, JBIC Journal of Biological Inorganic Chemistry.

[8]  Scott E. Fraser,et al.  A SMART MAGNETIC RESONANCE IMAGING AGENT THAT REPORTS ON SPECIFIC ENZYMATIC ACTIVITY , 1997 .

[9]  Craig R Malloy,et al.  MRI thermometry based on PARACEST agents. , 2005, Journal of the American Chemical Society.

[10]  P. Anelli,et al.  Sulfonamide‐Functionalized Gadolinium DTPA Complexes as Possible Contrast Agents for MRI: A Relaxometric Investigation , 2000 .

[11]  B. Bleaney.  Nuclear magnetic resonance shifts in solution due to lanthanide ions , 1972 .

[12]  M. Botta,et al.  NMR, Relaxometric, and Structural Studies of the Hydration and Exchange Dynamics of Cationic Lanthanide Complexes of Macrocyclic Tetraamide Ligands , 1999 .

[13]  A Dean Sherry,et al.  Selective sensing of zinc ions with a PARACEST contrast agent. , 2005, Angewandte Chemie.

[14]  Robert J Gillies,et al.  High resolution pHe imaging of rat glioma using pH‐dependent relaxivity , 2006, Magnetic resonance in medicine.

[15]  Enzo Terreno,et al.  Contrast agents for magnetic resonance angiographic applications: 1H and 17O NMR relaxometric investigations on two gadolinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin , 1999, JBIC Journal of Biological Inorganic Chemistry.

[16]  M. Botta,et al.  Prototropic vs Whole Water Exchange Contributions to the Solvent Relaxation Enhancement in the Aqueous Solution of a Cationic Gd3+ Macrocyclic Complex , 1997 .

[17]  S. Bott,et al.  Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent: the effect of other ligating groups on dissociation of a p-nitrophenolic pendant arm. , 2004, Journal of the American Chemical Society.

[18]  A. Sherry,et al.  Unusually sharp dependence of water exchange rate versus lanthanide ionic radii for a series of tetraamide complexes. , 2002, Journal of the American Chemical Society.

[19]  A Dean Sherry,et al.  Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. , 2006, Chemical Society reviews.

[20]  M. Botta,et al.  A macromolecular Gd(III) complex as pH-responsive relaxometric probe for MRI applications , 1999 .

[21]  K. Bhakoo,et al.  Application of MRI to Cell Tracking , 2008 .

[22]  Enzo Terreno,et al.  Paramagnetic Lanthanide(III) complexes as pH‐sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications , 2002, Magnetic resonance in medicine.

[23]  R S Balaban,et al.  A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). , 2000, Journal of magnetic resonance.

[24]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[25]  Jeff W M Bulte,et al.  Monitoring cell therapy using iron oxide MR contrast agents. , 2004, Current pharmaceutical biotechnology.

[26]  A. Sherry,et al.  A novel europium(III)-based MRI contrast agent. , 2001, Journal of the American Chemical Society.

[27]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[28]  A Dean Sherry,et al.  Cyclen-based phenylboronate ligands and their Eu3+ complexes for sensing glucose by MRI. , 2004, Bioconjugate chemistry.

[29]  A. Sherry,et al.  1H and (17)O NMR detection of a lanthanide-bound water molecule at ambient temperatures in pure water as solvent. , 2001, Inorganic chemistry.

[30]  Jinyuan Zhou,et al.  Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly‐L‐lysine and a starburst dendrimer , 2006, Magnetic resonance in medicine.

[31]  Claudio Luchinat,et al.  Mechanistic studies of a calcium-dependent MRI contrast agent. , 2002, Inorganic chemistry.

[32]  Peter Caravan,et al.  Protein binding to lanthanide(III) complexes can reduce the water exchange rate at the lanthanide. , 2007, Inorganic chemistry.

[33]  Christian Hilty,et al.  Molecular Imaging Using a Targeted Magnetic Resonance Hyperpolarized Biosensor , 2006, Science.

[34]  M. Bouchiat,et al.  Nuclear Polarization in He 3 Gas Induced by Optical Pumping and Dipolar Exchange , 1960 .

[35]  J. Frank,et al.  Cellular magnetic resonance imaging: current status and future prospects , 2006, Expert review of medical devices.

[36]  Grace Hu,et al.  Molecular MR imaging of melanoma angiogenesis with ανβ3‐targeted paramagnetic nanoparticles , 2005, Magnetic resonance in medicine.

[37]  J. Meaney.  Magnetic resonance angiography of the peripheral arteries: current status , 2003, European Radiology.

[38]  S. Forsén,et al.  Study of Moderately Rapid Chemical Exchange Reactions by Means of Nuclear Magnetic Double Resonance , 1963 .

[39]  Enzo Terreno,et al.  Ln(III)-DOTAMGly Complexes: A Versatile Series to Assess the Determinants of the Efficacy of Paramagnetic Chemical Exchange Saturation Transfer Agents for Magnetic Resonance Imaging Applications , 2004, Investigative radiology.

[40]  A. Ceulemans,et al.  Room-temperature magnetic anisotropy of lanthanide complexes: A model study for various coordination polyhedra , 2002 .

[41]  Paul Jurek,et al.  Potentiometric and relaxometric properties of a gadolinium-based MRI contrast agent for sensing tissue pH. , 2007, Inorganic chemistry.

[42]  J. Klaveness,et al.  Synthesis and physicochemical characterisation of new amphiphilic gadolinium DO3A complexes as contrast agents for MRI , 2000 .

[43]  Byunghee Yoo,et al.  A PARACEST MRI contrast agent to detect enzyme activity. , 2006, Journal of the American Chemical Society.

[44]  M. Botta,et al.  DEPENDENCE OF THE RELAXIVITY AND LUMINESCENCE OF GADOLINIUM AND EUROPIUM AMINO-ACID COMPLEXES ON HYDROGENCARBONATE AND PH , 1999 .

[45]  N Jon Shah,et al.  Hyperpolarized xenon in NMR and MRI. , 2004, Physics in medicine and biology.

[46]  A. Sherry,et al.  Spectral properties of a bifunctional PARACEST europium chelate: an intermediate for targeted imaging applications. , 2007, Contrast media & molecular imaging.

[47]  L. Helm,et al.  Oxygen-17 NMR study of water exchange on gadolinium polyaminopolyacetates [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]- related to NMR imaging , 1993 .

[48]  Janet R Morrow,et al.  Europium(III) macrocyclic complexes with alcohol pendant groups as chemical exchange saturation transfer agents. , 2006, Journal of the American Chemical Society.

[49]  Peter Caravan,et al.  Enzyme-Activated Gd3+ Magnetic Resonance Imaging Contrast Agents with a Prominent Receptor-Induced Magnetization Enhancement. , 2001, Angewandte Chemie.

[50]  H. Puschmann,et al.  Bidentate lactate binding in aqueous solution in a cationic, heptadentate lanthanide complex: an effective chiral derivatising agent. , 2001, Chemical communications.

[51]  J. Klaveness,et al.  Preparation and in vitro evaluation of GdDOTA-(BOM)4; a novel angiographic MRI contrast agent. , 2003, Organic & biomolecular chemistry.

[52]  M. Pagel,et al.  Peptidyl molecular imaging contrast agents using a new solid-phase peptide synthesis approach. , 2007, Bioconjugate chemistry.

[53]  Robert J Gillies,et al.  Renal and systemic pH imaging by contrast‐enhanced MRI , 2003, Magnetic resonance in medicine.

[54]  Kejia Cai,et al.  Targeted PARACEST nanoparticle contrast agent for the detection of fibrin , 2006, Magnetic resonance in medicine.

[55]  M. Botta,et al.  Direct NMR Spectroscopic Observation of a Lanthanide-Coordinated Water Molecule whose Exchange Rate Is Dependent on the Conformation of the Complexes. , 1998, Angewandte Chemie.

[56]  C. Thomsen,et al.  Peripheral vascular surgery and magnetic resonance arteriography--a review. , 2001, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[57]  Peter Caravan,et al.  The interaction of MS-325 with human serum albumin and its effect on proton relaxation rates. , 2002, Journal of the American Chemical Society.

[58]  D. Parker,et al.  Controllable pH modulation of lanthanide luminescenceby intramolecular switching of the hydration state , 2000 .

[59]  T. Gunnlaugsson,et al.  Reversible anion binding in aqueous solution at a cationic heptacoordinate lanthanide centre: selective bicarbonate sensing by time-delayed luminescence , 1998 .

[60]  Matthew E Merritt,et al.  Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI , 2005, Magnetic resonance in medicine.

[61]  C. Dobson,et al.  Origin of lanthanide nuclear magnetic resonance shifts and their uses , 1972 .

[62]  Xavier Golay,et al.  Amide proton transfer imaging of human brain tumors at 3T , 2006, Magnetic resonance in medicine.

[63]  A Dean Sherry,et al.  The amide protons of an ytterbium(III) dota tetraamide complex act as efficient antennae for transfer of magnetization to bulk water. , 2002, Angewandte Chemie.

[64]  A Dean Sherry,et al.  A paramagnetic CEST agent for imaging glucose by MRI. , 2003, Journal of the American Chemical Society.

[65]  A. Sherry,et al.  Modulation of water exchange in europium(III) DOTA-tetraamide complexes via electronic substituent effects. , 2008, Journal of the American Chemical Society.

[66]  A. Kassner,et al.  Molecular Imaging of Angiogenesis in Nascent Vx-2 Rabbit Tumors Using a Novel ανβ3-targeted Nanoparticle and 1.5 Tesla Magnetic Resonance Imaging , 2003 .

[67]  T. Kodadek,et al.  Magnetic resonance imaging detects a specific peptide-protein binding event. , 2002, Journal of the American Chemical Society.

[68]  Peter C M van Zijl,et al.  Sensitive CEST agents based on nucleic acid imino proton exchange: Detection of poly(rU) and of a dendrimer‐poly(rU) model for nucleic acid delivery and pharmacology , 2003, Magnetic resonance in medicine.

[69]  H. Mcconnell,et al.  Molecular Transfer of Nonequilibrium Nuclear Spin Magnetization , 1957 .

[70]  A. Sherry,et al.  Albumin-binding PARACEST agents , 2007, JBIC Journal of Biological Inorganic Chemistry.

[71]  E. Terreno,et al.  Gd-loaded liposomes as T1, susceptibility, and CEST agents, all in one. , 2007, Journal of the American Chemical Society.

[72]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[73]  Robert E Lenkinski,et al.  PARACEST agents: modulating MRI contrast via water proton exchange. , 2003, Accounts of chemical research.

[74]  Craig H Meyer,et al.  Technology Insight: in vivo cell tracking by use of MRI , 2006, Nature Clinical Practice Cardiovascular Medicine.

[75]  J. Bulte,et al.  Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange. , 2001, Journal of the American Chemical Society.

[76]  R S Balaban,et al.  Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST) , 2000, Magnetic resonance in medicine.

[77]  S. Fraser,et al.  A Calcium-Sensitive Magnetic Resonance Imaging Contrast Agent , 1999 .

[78]  Peter C M van Zijl,et al.  MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST) , 2007, Proceedings of the National Academy of Sciences.