Physical Sciences and Mathematics Commons^™

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 …

Designing A More Effective Mri Contrast Agent: Investigation Into Various Functionalization Strategies For Targeted Imaging, Lauren Nicole Rust

Dissertations and Theses

Magnetic resonance imaging (MRI) is a medical imaging technique that provides high-resolution images used for diagnostic medicine while maintaining a superior safety profile compared to other radiative techniques. The administration of gadolinium-based contrast agents (GBCAs) improves the diagnostic power of MRI and have been used clinically for over three decades. Although GBCAs are effective at improving the contrast in the image, their detection limits are high and require a large dose to generate an observable effect. This high dose is the consequence of the current available designs of clinical GBCAs; their structures are not tuned to generate optimal efficacy. Efficacy …

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 B_¹ 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

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.

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

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

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 …

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

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

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

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

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

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

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

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

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

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

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 …

Synthesis And Evaluation Of Lanthanide Ion Dota-Tetraamide Complexes Bearing Peripheral Hydroxyl Groups, Azhar Pasha, Mai Lin, Gyula Tircso, Cynthia L. Rostollan, Mark Woods, Garry Kiefer, A. Dean Sherry, Xiankai Sun

Chemistry Faculty Publications and Presentations

The use of lanthanide-based contrast agents for magnetic resonance imaging has become an integral component of this important diagnostic modality. These inert chelates typically possess high thermodynamic stability constants that serve as a predictor for in vivo stability and low toxicity. Recently, a new class of contrast agents was reported having a significantly lower degree of thermodynamic stability while exhibiting biodistribution profiles indicative of high stability under biological conditions. These observations are suggestive that the nature of contrast agent stability is also dependent upon the kinetics of complex dissociation, a feature of potential importance when contemplating the design of new …

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

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 …

Polymeric Paracest Agents For Enhancing Mri Contrast Sensitivity, Yunkou Wu, Youfu Zhou, Olivier Quari, Mark Woods, Piyu Zhao, Todd B. Soesbe, Garry Kiefer, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Linear polymers of PARACEST agents were prepared by using classical free radical chain polymerization conditions. The Eu³⁺-polymers exhibited similar intermediate-to-slow water exchange and CEST characteristics as the Eu³⁺-monomers. This provided an avenue to lower the detection limit of these imaging agents substantially and makes them potentially useful as MRI sensors for molecular imaging.

Towards The Rational Design Of Mri Contrast Agents: Electron Spin Relaxation Is Largely Unaffected By The Coordination Geometry Of Gadolinium(Iii)–Dota-Type Complexes, Alain Borel, Jonathan F. Bean, Robert B. Clarkson, Lothar Helm, Loïck Moriggi, A. Dean Sherry, Mark Woods

Chemistry Faculty Publications and Presentations

Electron‐spin relaxation is one of the determining factors in the efficacy of MRI contrast agents. Of all the parameters involved in determining relaxivity it remains the least well understood, particularly as it relates to the structure of the complex. One of the reasons for the poor understanding of electron‐spin relaxation is that it is closely related to the ligand‐field parameters of the Gd³⁺ ion that forms the basis of MRI contrast agents and these complexes generally exhibit a structural isomerism that inherently complicates the study of electron spin relaxation. We have recently shown that two DOTA‐type ligands could be …

Modulation Of Water Exchange In Europium(Iii) Dota–Tetraamide Complexes Via Electronic Substituent Effects, S. James Ratnakar, Mark Woods, Angelo J.M. Lubag, Zoltan Kovacs, A. Dean Sherry

Chemistry Faculty Publications and Presentations

The chemical exchange saturation transfer (CEST) efficiency for a series Eu³⁺-based tetraamide complexes bearing p-substituents on a single coordinating pendant arm is highly sensitive to water exchange rates. The CEST effect increases in the order Me < MeO < F ∼ CO₂^tBu < CN ≪ H. These results show that CEST contrast can be modulated by changes in electron density at a single ligating atom, and this forms the basis of creating imaging agents that respond to chemical oxidation and reduction.

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

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 …

A Bridge To Coordination Isomer Selection In Lanthanide(Iii) Dota-Tetraamide Complexes, Jeff Vipond, Mark Woods, Piyu Zhao, Gyula Tircsó, Jimin Ren, Simon G. Bott, Doug Ogrin, Garry Kiefer, Zoltan Kovacs, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O₂-bridged-DOTAM was synthesized in a 34% yield from cyclen. …

Europium(Iii) Macrocyclic Complexes With Alcohol Pendant Groups As Chemical Exchange Saturation Transfer Agents, Mark Woods, Donald E. Woessner, Piyu Zhao, Azhar Pasha, Meng-Yin Yang, Ching-Hui Huang, Olga Vasalatiy, Janet R. Morrow, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Paramagnetic lanthanide(III) complexes that contain hyperfine-shifted exchangeable protons offer considerable advantages over diamagnetic molecules as chemical exchange saturation transfer (CEST) agents for MRI. As part of a program to investigate avenues to improve the sensitivity of such agents, the CEST characteristics of europium(III) macrocyclic complexes having appended hydroxyethyl groups were investigated. The CEST spectrum of the asymmetrical complex, EuCNPHC³⁺, shows five distinct peaks for each magnetically nonequivalent exchangeable proton in the molecule. The CEST spectra of this complex were fitted to NMR Bloch theory to yield exchange rates between each of six exchanging proton pools (five on the …

Toward The Design Of Mr Agents For Imaging Β-Cell Function, Mark Woods, Shanrong Zhang, A. Dean Sherry

Chemistry Faculty Publications and Presentations

The chemistry of Gd3+-based MRI agents has advanced considerably during the past decade toward agents with higher relaxivity and agents that respond to physiology and / or metabolism. This review describes various approaches that have been taken toward the development of responsive contrast agents and discusses the importance of fast water exchange for advancement of targeted Gd3+-based agents with higher sensitivity. The recent discovery of Eu3+ complexes having extraordinarily slow water exchange has opened a new avenue in contrast agent design based upon the chemical exchange saturation transfer (CEST) mechanism. These new paramagnetic complexes called PARACEST agents offer new possibilities …

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, Mark Woods, Garry Kiefer, Simon G. Bott, Aminta Castillo-Muzquiz, Carrie Eshelbrenner, Lydie Michaudet, Kenneth Mcmillan, Siva D.K. Mudigunda, Doug Ogrin, Gyula Tircso, Shanrong Zhang, Piyu Zhao, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triAcetate) and GdNP-DO3AM (1-methlyene(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide), containing a single nitrophenolic pendant arm plus either three acetate or three amide pendant arms were synthesized and characterized. The properties of the gadolinium, terbium, and dysprosium complexes of these ligands were examined as a function of pH. The extent and mechanism of the changes in water relaxivity with pH of each gadolinium complex was found to differ substantially for the two complexes. The water relaxivity of Gd(NP-DO3A) increases from 4.1 …