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Articles 1 - 27 of 27
Full-Text Articles in Physical Sciences and Mathematics
Designing Environmentally Responsible And Highly Effective Bioorthogonally Functionalized Chiral Mri Contrast Agents, Karley Breann Maier
Designing Environmentally Responsible And Highly Effective Bioorthogonally Functionalized Chiral Mri Contrast Agents, Karley Breann Maier
Dissertations and Theses
Magnetic resonance imaging (MRI) revolutionized diagnostic imaging and modernized the characterization of numerous diseases. The clinical success of MRI is in large part due to the employment of gadolinium-based contrast agents (GBCAs). Due to sensitivity limitations, GBCAs are indicated at markedly high dosages (~1 g Gd3+ per exam). The routine use of such large quantities of gadolinium poses significant health and environmental risks. There are growing concerns over the effects of dechelation of the metal in vivo and the possible effect of resulting gadolinium deposition. Concurrently, there is a rising awareness of gadolinium anomalies borne by GBCAs which undergo …
Steady-State Transmembrane Water Exchange In Proliferating Cultures Of Saccharomyces Cerevisiae, Joseph O'Malley Armstrong
Steady-State Transmembrane Water Exchange In Proliferating Cultures Of Saccharomyces Cerevisiae, Joseph O'Malley Armstrong
Dissertations and Theses
Cellular water exchange is often considered in terms of a change in volume, where a net flux of water moves across the cell membrane due to a change in osmotic pressure. Osmotic pressure can cause a cell to shrink or swell, however, rapid water exchange persists across the membrane even when the volume of the cell is constant. Steady-state transmembrane water exchange describes the exchange of water across the cell membranes which results in no net change in cell volume. This exchange is astonishingly rapid; the entire pool of intracellular water of a Saccharomyces cerevisiae cell may exchange 2-5 times …
Genetically Encoded Phase Contrast Agents For Digital Holographic Microscopy, Arash Farhadi, Manuel Bedrossian, Justin Lee, Gabrielle H. Ho, Mikhail G. Shapiro, Jay Nadeau
Genetically Encoded Phase Contrast Agents For Digital Holographic Microscopy, Arash Farhadi, Manuel Bedrossian, Justin Lee, Gabrielle H. Ho, Mikhail G. Shapiro, Jay Nadeau
Physics Faculty Publications and Presentations
Quantitative phase imaging and digital holographic microscopy have shown great promise for visualizing the motion, structure and physiology of microorganisms and mammalian cells in three dimensions. However, these imaging techniques currently lack molecular contrast agents analogous to the fluorescent dyes and proteins that have revolutionized fluorescence microscopy. Here we introduce the first genetically encodable phase contrast agents based on gas vesicles. The relatively low index of refraction of the air-filled core of gas vesicles results in optical phase advancement relative to aqueous media, making them a “positive” phase contrast agent easily distinguished from organelles, dyes, or microminerals. We demonstrate this …
Controlling Water Exchange Kinetics And Improving Paracest Imaging, Jacqueline R. Slack
Controlling Water Exchange Kinetics And Improving Paracest Imaging, Jacqueline R. Slack
Dissertations and Theses
Generating MR image contrast from exogenous contrast media through chemical exchange saturation transfer (CEST) offers several exciting new possibilities, such as multicolored imaging, the interleaving of pre- and post-contrast images, and the potential to perform ratiometric metabolic imaging. The major limitation of the deployment of CEST imaging is the comparatively high detection limits of exogenous agents and particularly at the low B1 power levels required to meet SAR requirements. The large chemical shifts afforded by paramagnetic (paraCEST) agents permit more rapid exchange kinetics and therefore potentially more effective contrast agents. Despite comparatively large chemical shifts, many Ln3+ DOTA-tetraamide …
Investigations Into The Effects Of Water Exchange And The Structure Of Lanthanide Chelates, Katherine Marie Payne
Investigations Into The Effects Of Water Exchange And The Structure Of Lanthanide Chelates, Katherine Marie Payne
Dissertations and Theses
Lanthanide chelates are effective agents for improving contrast in MR images. Optimizing the relaxation of inner sphere water molecules is a common focus of research in this field. However, the efforts to design an optimal contrast agent have commonly over-looked the relationship of water position and water exchange kinetics. This work explores structural conformation, the impact of very fast water exchange kinetics on hydration, and differing tumbling rates for regioisomers of a number of lanthanide chelates. We have grown crystals of LnDOTMA and obtained structural data by X-ray diffraction that provide a picture of the chelate during water exchange and …
Relative Sensitivities Of Dce-Mri Pharmacokinetic Parameters To Arterial Input Function (Aif) Scaling, Xin Li, Yu Cai, Brendan Moloney, Yiyi Chen, Wei Huang, Mark Woods, Fergus V. Coakley, William D. Rooney, Mark G. Garzotto, Charles S. Springer Jr.
Relative Sensitivities Of Dce-Mri Pharmacokinetic Parameters To Arterial Input Function (Aif) Scaling, Xin Li, Yu Cai, Brendan Moloney, Yiyi Chen, Wei Huang, Mark Woods, Fergus V. Coakley, William D. Rooney, Mark G. Garzotto, Charles S. Springer Jr.
Chemistry Faculty Publications and Presentations
Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has been used widely for clinical applications. Pharmacokinetic modeling of DCE-MRI data that extracts quantitative contrast reagent/tissue-specific model parameters is the most investigated method. One of the primary challenges in pharmacokinetic analysis of DCE-MRI data is accurate and reliable measurement of the arterial input function (AIF), which is the driving force behind all pharmacokinetics. Because of effects such as inflow and partial volume averaging, AIF measured from individual arteries sometimes require amplitude scaling for better representation of the blood contrast reagent (CR) concentration time-courses. Empirical approaches like blinded AIF estimation or reference tissue AIF derivation …
Expanding The Versatility Of Nano Assembled Capsules As Platform Of Potential High Payload Mri Contrast Agents, Annah Farashishiko
Expanding The Versatility Of Nano Assembled Capsules As Platform Of Potential High Payload Mri Contrast Agents, Annah Farashishiko
Dissertations and Theses
Magnetic resonance imaging (MRI) has become a powerful clinical modality in diagnostic medicine. It is non-invasive and offers high spatial and temporal resolution. The goal of molecular imaging is to reveal the pathophysiology underlying the observed anatomy and diagnose diseases. The detection of pathological biomarkers can lead to early recognition of diseases and improved monitoring for recurrence. Clinically available contrast agents are limited in their discrimination of contrast between tissues and they tend to have very high detection limits. Because biomarkers are very low in concentration there is a need for high payload deposition of contrast agent (CA) and targeted …
Human Whole-Blood (1)H2o Longitudinal Relaxation With Normal And High-Relaxivity Contrast Reagents: Influence Of Trans-Cell-Membrane Water Exchange, Gregory J. Wilson, Mark Woods, Charles S. Springer Jr., Sarah Bastawrous, Puneet Bhargava, Jeffrey H. Maki
Human Whole-Blood (1)H2o Longitudinal Relaxation With Normal And High-Relaxivity Contrast Reagents: Influence Of Trans-Cell-Membrane Water Exchange, Gregory J. Wilson, Mark Woods, Charles S. Springer Jr., Sarah Bastawrous, Puneet Bhargava, Jeffrey H. Maki
Chemistry Faculty Publications and Presentations
PURPOSE: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R1 ) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.
METHODS: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.
RESULTS: In plasma, the 1H2 O R …
The Confluence Of Structure And Dynamics In Lanthanide(Iii) Chelates: How Dynamics Help Define Structure In Solution, Benjamin Charles Webber, Mark Woods
The Confluence Of Structure And Dynamics In Lanthanide(Iii) Chelates: How Dynamics Help Define Structure In Solution, Benjamin Charles Webber, Mark Woods
Chemistry Faculty Publications and Presentations
Coordination exchange processes tend to dominate the solution state behaviour of lanthanide chelates and generally prohibit the study of small conformational changes. In this article we take advantage of coordinatively rigid Eu3+ chelates to examine the small conformational changes that occur in these chelates as water dissociatively exchanges in and out of the inner coordination sphere. The results show that the time-averaged conformation of the chelate alters as the water exchange rate increases. This conformational change reflects a change in the hydration state (q/rLnH6) of the chelate. The hydration state has recently come …
Coupling Fast Water Exchange To Slow Molecular Tumbling In Gd3+ Chelates: Why Faster Is Not Always Better, Stefano Avedano, Mauro Botta, Julian Saunders Haigh, Dario L. Lango, Mark Woods
Coupling Fast Water Exchange To Slow Molecular Tumbling In Gd3+ Chelates: Why Faster Is Not Always Better, Stefano Avedano, Mauro Botta, Julian Saunders Haigh, Dario L. Lango, Mark Woods
Chemistry Faculty Publications and Presentations
The influence of dynamics on solution state structure is a widely overlooked consideration in chemistry. Variations in Gd3+ chelate hydration with changing coordination geometry and dissociative water exchange kinetics substantially impact the effectiveness (or relaxivity) of monohydrated Gd3+ chelates as T1-shortening contrast agents for MRI. Theory shows that relaxivity is highly dependent upon the Gd3+–water proton distance (rGdH), and yet this distance is almost never considered as a variable in assessing the relaxivity of a Gd3+ chelate as a potential contrast agent. The consequence of this omission can be seen when considering …
Chemical Exchange Saturation Transfer Is Unaffected By Modest Changes In Pressure, Benjamin Charles Webber, Christiane A. Carney, Mark Woods
Chemical Exchange Saturation Transfer Is Unaffected By Modest Changes In Pressure, Benjamin Charles Webber, Christiane A. Carney, Mark Woods
Chemistry Faculty Publications and Presentations
ParaCEST (paramagnetic Chemical Exchange Saturation Transfer) agents offer an unparalleled opportunity to perform quantitative molecular imaging by MRI. Agents that can alter the image contrast they generate in response to changes in local environmental parameters such as pH, glucose concentration or lactate concentration can be used ratiometrically to quantitatively describe the local tissue environment. However, when performing such quantitative measurements it is important that the results are not confounded by changes in a second environmental parameter. In vivo pressure varies quite considerably, both through the respiratory cycle and from tissue to tissue (tumors in particular have high interstitial pressures). Since …
Properties, Solution State Behavior, And Crystal Structures Of Chelates Of Dotma, Silvio Aime, Mauro Botta, Zoltán Garda, Benjamin E. Kucera, Gyula Tircso, Victor G. Young, Mark Woods
Properties, Solution State Behavior, And Crystal Structures Of Chelates Of Dotma, Silvio Aime, Mauro Botta, Zoltán Garda, Benjamin E. Kucera, Gyula Tircso, Victor G. Young, Mark Woods
Chemistry Faculty Publications and Presentations
The chemistry of polyamino carboxylates and their use as ligands for Ln(3+) ions is of considerable interest from the point of view of the development of new imaging agents. Of particular interest is the chemistry of the macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and its derivatives. Herein we report that the tetramethylated DOTA derivative, DOTMA, possess several properties that, from an imaging agent development point of view, are more advantageous than those of the parent DOTA. In particular, the Ln(3+) chelates of DOTMA exhibit a marked preference for the monocapped twisted square antiprismatic coordination isomer which imparts more rapid water exchange …
Towards The Rational Design Of Mri Contrast Agents: Δ-Substitution Of Lanthanide(Iii) Nb-Dota-Tetraamide Chelates Influences But Does Not Control Coordination Geometry, Christiane E. Carney, Anh D. Tran, Jing Wang, Matthias C. Schabel, A. Dean Sherry, Mark Woods
Towards The Rational Design Of Mri Contrast Agents: Δ-Substitution Of Lanthanide(Iii) Nb-Dota-Tetraamide Chelates Influences But Does Not Control Coordination Geometry, Christiane E. Carney, Anh D. Tran, Jing Wang, Matthias C. Schabel, A. Dean Sherry, Mark Woods
Chemistry Faculty Publications and Presentations
LnDOTA-tetraamide chelates (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) have received considerable recent attention as a result of their potential to act as PARACEST contrast agents for magnetic resonance imaging (MRI). Although PARACEST agents afford several advantages over conventional contrast agents they suffer from substantially higher detection limits; thus, improving the effectiveness of LnDOTA-tetraamide chelates is an important goal. In this study we investigate the potential to extend conformational control of LnDOTA-type ligands to those applicable to PARACEST. Furthermore, the question of whether δ- rather than α-substitution of the pendant arms could be used to control the chelate coordination geometry is addressed. Although δ-substitution does …
Analysis Of The Conformational Behavior And Stability Of The Sap And Tsap Isomers Of Lanthanide(Iii) Nb-Dota-Type Chelates, Gyula Tircso, Benjamin Charles Webber, Benjamin E. Kucera, Victor G. Young, Mark Woods
Analysis Of The Conformational Behavior And Stability Of The Sap And Tsap Isomers Of Lanthanide(Iii) Nb-Dota-Type Chelates, Gyula Tircso, Benjamin Charles Webber, Benjamin E. Kucera, Victor G. Young, Mark Woods
Chemistry Faculty Publications and Presentations
Controlling the water exchange kinetics of macrocyclic Gd(3+) chelates, a key parameter in the design of improved magnetic resonance imaging (MRI) contrast media, may be facilitated by selecting the coordination geometry of the chelate. The water exchange kinetics of the mono- capped twisted square antiprism (TSAP) being much closer to optimal than those of the mono capped square antiprism (SAP) render the TSAP isomer more desirable for high relaxivity applications. Two systems have been developed that allow for selection of the TSAP coordination geometry in 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd(3+) chelates, both based upon the macrocycle nitrobenzyl cyclen. In this paper …
Investigations Into Whole Water, Prototropic And Amide Proton Exchange In Lanthanide(Iii) Dota-Tetraamide Chelates, Mark Woods, Azhar Pasha, Piyu Zhao, Gyula Tircso, Somdatta Chowdhury, Garry Kiefer, Donald E. Woessner, A. Dean Sherry
Investigations Into Whole Water, Prototropic And Amide Proton Exchange In Lanthanide(Iii) Dota-Tetraamide Chelates, Mark Woods, Azhar Pasha, Piyu Zhao, Gyula Tircso, Somdatta Chowdhury, Garry Kiefer, Donald E. Woessner, A. Dean Sherry
Chemistry Faculty Publications and Presentations
Lanthanide(III) chelates of DOTA-tetraamide ligands have been an area of particular interest since the discovery that water exchange kinetics are dramatically affected by the switch from acetate to amide side-chain donors. More recently these chelates have attracted interest as potential PARACEST agents for use in MRI. In this paper we report the results of studies using chemical exchange saturation transfer (CEST) and some more recently reported chelates to re-examine the exchange processes in this class of chelate. We find that the conclusions of Parker and Aime are, for the most part, solid; water exchange is slow and a substantial amount …
Strategies For Labeling Proteins With Paracest Agents, Olga Vasalatiy, Piyu Zhao, Mark Woods, Andrei Marconescu, Aminta Castillo-Muzquiz, Philip Thorpe, Garry Kiefer, A. Dean Sherry
Strategies For Labeling Proteins With Paracest Agents, Olga Vasalatiy, Piyu Zhao, Mark Woods, Andrei Marconescu, Aminta Castillo-Muzquiz, Philip Thorpe, Garry Kiefer, A. Dean Sherry
Chemistry Faculty Publications and Presentations
Reactive surface lysine groups on the chimeric monoclonal antibody (3G4) and on human serum albumin (HSA) were labeled with two different PARACEST chelates. Between 7.4 – 10.1 chelates were added per 3G4 molecule and between 5.6 – 5.9 chelates per molecule of HSA, depending upon which conjugation chemistry was used. The immunoreactivity of 3G4 as measured by ELISA assays was highly dependent upon the number of attached chelates: 88% immunoreactivity with 7.4 chelates per antibody versus only 17% immunoreactivity with 10.1 chelates per antibody. Upon conjugation to 3G4, the bound water lifetime of Eu-1 increased only marginally, up from …
Imaging The Extracellular Ph Of Tumors By Mri After Injection Of A Single Cocktail Of T1 And T2 Contrast Agents, Gary V. Martinez, Xiaomeng Zhang, María L. García-Martín, David L. Morse, Mark Woods, A. Dean Sherry, Robert J. Gillies
Imaging The Extracellular Ph Of Tumors By Mri After Injection Of A Single Cocktail Of T1 And T2 Contrast Agents, Gary V. Martinez, Xiaomeng Zhang, María L. García-Martín, David L. Morse, Mark Woods, A. Dean Sherry, Robert J. Gillies
Chemistry Faculty Publications and Presentations
The extracellular pH (pH(e) ) of solid tumors is acidic, and there is evidence that an acidic pH(e) is related to invasiveness. Herein, we describe an MRI single-infusion method to measure pH(e) in gliomas using a cocktail of contrast agents (CAs). The cocktail contained gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (GdDOTA-4AmP) and dysprosium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetrakis(methylenephosphonic acid) (DyDOTP), whose effects on relaxation are sensitive and insensitive to pH, respectively. The Gd-CA dominated the spin-lattice relaxivity ΔR(1) , whereas the Dy-CA dominated the spin-spin relaxivity ΔR(2)*. The ΔR(2)* effects were used to determine the pixel-wise concentration of [Dy] which, in turn, was used to calculate a value for [Gd] …
The Population Of Sap And Tsap Isomers In Cyclen-Based Lanthanide(Iii) Chelates Is Substantially Affected By Solvent, Kyle J. Miller, Ali A. Saherwala, Benjamin C. Webber, Yunkou Wu, A. Dean Sherry, Mark Woods
The Population Of Sap And Tsap Isomers In Cyclen-Based Lanthanide(Iii) Chelates Is Substantially Affected By Solvent, Kyle J. Miller, Ali A. Saherwala, Benjamin C. Webber, Yunkou Wu, A. Dean Sherry, Mark Woods
Chemistry Faculty Publications and Presentations
The square antiprism/twisted square antiprism ratio in LnDOTA-tetraamide chelates is a critical parameter in governing water-exchange kinetics and ultimately the utility of a chelate as a PARACEST MRI contrast agent. In LnDOTA-tetraamide chelates with tertiary amides, this ratio and the rate of interconversion between these two structural isomers are found to be dramatically dependent upon the solvent and possibly other local environmental factors.
Cest And Paracest Mr Contrast Agents, Ileana Hancu, W. Thomas Dixon, Mark Woods, Elena Vinogradov, A. Dean Sherry, Robert E. Lenkinski
Cest And Paracest Mr Contrast Agents, Ileana Hancu, W. Thomas Dixon, Mark Woods, Elena Vinogradov, A. Dean Sherry, Robert E. Lenkinski
Chemistry Faculty Publications and Presentations
In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and …
Polymeric Paracest Mri Contrast Agents As Potential Reporters For Gene Therapy, Yunkou Wu, Christiane E. Carney, Michael Denton, Elaine Hart, Piyu Zhao, Daniel N. Streblow, A. Dean Sherry, Mark Woods
Polymeric Paracest Mri Contrast Agents As Potential Reporters For Gene Therapy, Yunkou Wu, Christiane E. Carney, Michael Denton, Elaine Hart, Piyu Zhao, Daniel N. Streblow, A. Dean Sherry, Mark Woods
Chemistry Faculty Publications and Presentations
Gene therapy is a potentially powerful treatment approach that targets molecular remedies for disease. Among other challenges it remains difficult to monitor gene delivery and its downstream metabolic consequences. Approaches to MRI gene reporters have been reported but few have the potential for translation beyond isolated cell systems. Herein, we report a polycationic polymer MRI contrast agent that binds to DNA in a ratio of one monomer unit per phosphate group of DNA. Significantly, this binding event diminishes the MR contrast signal from the agent itself potentially providing a platform for imaging delivery and release of a gene into cells …
Solid State And Solution Dynamics Of Pyridine Based Tetraaza- Macrocyclic Lanthanide Chelates Possessing Phosphonate Ligating Functionality (Ln-Pctmb): Effect On Relaxometry And Optical Properties, Garry Kiefer, Mark Woods
Solid State And Solution Dynamics Of Pyridine Based Tetraaza- Macrocyclic Lanthanide Chelates Possessing Phosphonate Ligating Functionality (Ln-Pctmb): Effect On Relaxometry And Optical Properties, Garry Kiefer, Mark Woods
Chemistry Faculty Publications and Presentations
The macrocyclic ligand 3,6,9-tris(methylenebutyl phosphonic acid)-3,6,9−15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene (PCTMB) was synthesized and complexes of Eu3+, Tb3+, and Gd3+ studied by X-ray crystallography, luminescence, and relaxometry. In the crystal these complexes are dimeric and possess 8-coordinate Ln3+ centers that are linked by bridging phosphonates. The rigidity introduced by the pyridyl nucleus forces the EuPCTMB and TbPCTMB to adopt a twisted snub disphenoid (TSD) coordination geometry. Examination of the 5D0 → 7F0 luminescent transition of EuPCTMB in the solid state confirmed the existence of a single distinct Eu3+ coordination environment, whereas two …
Effect Of The Regiochemistry Of Butyl Amide Substituents On The Solution-State Structures Of Lanthanide(Iii) Dota-Tetraamide Complexes, Tomoyasu Mani, Gyula Tircsó, Piyu Zhao, A. Dean Sherry, Mark Woods
Effect Of The Regiochemistry Of Butyl Amide Substituents On The Solution-State Structures Of Lanthanide(Iii) Dota-Tetraamide Complexes, Tomoyasu Mani, Gyula Tircsó, Piyu Zhao, A. Dean Sherry, Mark Woods
Chemistry Faculty Publications and Presentations
The coordination geometry adopted by the lanthanide complexes of DOTA-tetraamides is a critical factor in determining their water exchange kinetics. Controlling the water exchange kinetics of DOTA-tetraamide complexes, and by extension their coordination geometry, is of particular interest because of the potential application of this class of complex as PARACEST MRI contrast agents. To facilitate the maximum CEST effect at the lowest pre-saturation powers much slower exchange kinetics are required than are commonly observed with these types of chelates. Complexes that adopt the more slowly exchanging square antiprismatic coordination geometry are therefore preferred; however, the factors that govern which coordination …
The Effect Of The Amide Substituent On The Biodistribution And Tolerance Of Lanthanide(Iii) Dota-Tetraamide Derivatives, Mark Woods, Peter Caravan, Carlos F.G.C. Geraldes, Matthew T. Greenfield, Garry Kiefer, Mai Lin, Kenneth Mcmillan, M. Isabel M. Prata, Ana C. Santos, Xiankai Sun, Jufeng Wang, Shanrong Zhang, Piyu Zhao, A. Dean Sherry
The Effect Of The Amide Substituent On The Biodistribution And Tolerance Of Lanthanide(Iii) Dota-Tetraamide Derivatives, Mark Woods, Peter Caravan, Carlos F.G.C. Geraldes, Matthew T. Greenfield, Garry Kiefer, Mai Lin, Kenneth Mcmillan, M. Isabel M. Prata, Ana C. Santos, Xiankai Sun, Jufeng Wang, Shanrong Zhang, Piyu Zhao, A. Dean Sherry
Chemistry Faculty Publications and Presentations
Objectives—Recent advances in the design of MRI contrast agents have rendered the lanthanide complexes of DOTA-tetraamide ligands of considerable interest, both as responsive MR agents and paramagnetic chemical exchange saturation transfer agents. The potential utility of these complexes for in vivo applications is contingent upon them being well tolerated by the body. The purpose of this study was to examine how the nature of the amide substituent, and in particular its charge, affected the fate of these chelates postinjection.
Materials and Methods—Complexes of 6 DOTA-tetraamide ligands were prepared in which the nature of the amide substituent was systematically …
Synthesis And Relaxometric Studies Of A Dendrimer‐Based Ph‐Responsive Mri Contrast Agent, M. Meser Ali, Mark Woods, Peter Caravan, Ana C.L. Opina, Marga Spiller, James C. Fettinger, A. Dean Sherry
Synthesis And Relaxometric Studies Of A Dendrimer‐Based Ph‐Responsive Mri Contrast Agent, M. Meser Ali, Mark Woods, Peter Caravan, Ana C.L. Opina, Marga Spiller, James C. Fettinger, A. Dean Sherry
Chemistry Faculty Publications and Presentations
The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the “on” state compared to that of the “off” state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the …
Potentiometric And Relaxometric Properties Of A Gadolinium-Based Mri Contrast Agent For Sensing Tissue Ph, Ferenc K. Kálmán, Mark Woods, Peter Caravan, Paul Jurek, Marga Spiller, Gyula Tircso, Róbert Király, Ernő Brücher, A. Dean Sherry
Potentiometric And Relaxometric Properties Of A Gadolinium-Based Mri Contrast Agent For Sensing Tissue Ph, Ferenc K. Kálmán, Mark Woods, Peter Caravan, Paul Jurek, Marga Spiller, Gyula Tircso, Róbert Király, Ernő Brücher, A. Dean Sherry
Chemistry Faculty Publications and Presentations
The pH-sensitive contrast agent, GdDOTA-4AmP (Gd1) has been successfully used to map tissue pH by MRI. Further studies now demonstrate that two distinct chemical forms of the complex can be prepared depending upon the pH at which Gd3+ is mixed with ligand 1. The desired pH-sensitive form of this complex, referred to here as a Type II complex, is obtained as the exclusive product only when the complexation reaction is performed above pH 8. At lower pH values, a second complex is formed that, by analogy with an intermediate formed during the preparation of GdDOTA, we tentatively assign …
Albumin-Binding Paracest Agents, M. Meser Ali, Mark Woods, Eul Hyun Suh, Zoltan Kovacs, Gyula Tircsó, Piyu Zhao, Vikram D. Kodibagkar, A. Dean Sherry
Albumin-Binding Paracest Agents, M. Meser Ali, Mark Woods, Eul Hyun Suh, Zoltan Kovacs, Gyula Tircsó, Piyu Zhao, Vikram D. Kodibagkar, A. Dean Sherry
Chemistry Faculty Publications and Presentations
Lanthanide complexes (Eu3+, Gd3+ and Yb3+) of two different 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid tetraamide derivatives containing two (2) and four (3) O-benzyl-L-serine amide substituents were synthesized and their chemical exchange saturation transfer (CEST) and relaxometric properties were examined in the presence and absence of human serum albumin (HSA). Both Eu2 and Eu3 display a significant CEST effect from a single slowly exchanging Eu3+-bound water molecule, making these PARACEST complexes potentially useful as vascular MRI agents. Yb2 also showed a detectable CEST effect from both the Yb3+-bound water protons and the …
Structural And Chiroptical Properties Of The Two Coordination Isomers Of Ybdota-Type Complexes, Lorenzo Di Bari, Gennaro Pescitelli, A. Dean Sherry, Mark Woods
Structural And Chiroptical Properties Of The Two Coordination Isomers Of Ybdota-Type Complexes, Lorenzo Di Bari, Gennaro Pescitelli, A. Dean Sherry, Mark Woods
Chemistry Faculty Publications and Presentations
Studies of the structural, physical, and chemical properties of the lanthanide(III) complexes of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and related ligands are often complicated by the presence of two coordination isomers in solution. Since these coordination isomers are in exchange and cannot be separated, many techniques offer information only on the weighted average of the two isomers. Lanthanide ion complexes formed with the ligands S(RRRR)NO2BnDOTMA and S(SSSS)NO2BnDOTMA preferentially adopt only one of the two common coordination isomers in solution, so the ytterbium complexes of these ligands offer a unique opportunity to study …