Author
Shanrong Zhang
Other affiliations: University of Texas at Austin, University of Texas at Dallas, University of Texas System
Bio: Shanrong Zhang is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: DOTA & Bound water. The author has an hindex of 25, co-authored 45 publications receiving 2478 citations. Previous affiliations of Shanrong Zhang include University of Texas at Austin & University of Texas at Dallas.
Topics: DOTA, Bound water, MRI contrast agent, Lanthanide, Neuroprotection
Papers
More filters
••
TL;DR: A theoretical framework based on the modified Bloch equations that relates the chemical properties of a CEST agent and various NMR parameters to the measured CEST effect was formulated, and results were in excellent agreement with experimental Z‐spectra obtained with an aqueous solution of a paramagnetic CESTAgent containing two different types of bound protons.
Abstract: Paramagnetic lanthanide complexes that display unusually slow water exchange between an inner sphere coordination site and bulk water may serve as a new class of MRI contrast agents with the use of chemical exchange saturation transfer (CEST) techniques. To aid in the design of paramagnetic CEST agents for reporting important biological indices in MRI measurements, we formulated a theoretical framework based on the modified Bloch equations that relates the chemical properties of a CEST agent (e.g., water exchange rates and bound water chemical shifts) and various NMR parameters (e.g., relaxation rates and applied B(1) field) to the measured CEST effect. Numerical solutions of this formulation for complex exchanging systems were readily obtained without algebraic manipulation or simplification. For paramagnetic CEST agents of the type used here, the CEST effect is relatively insensitive to the bound proton relaxation times, but requires a sufficiently large applied B(1) field to highly saturate the Ln(3+)-bound water protons. This in turn requires paramagnetic complexes with large Ln(3+)-bound water chemical shifts to avoid direct excitation of the exchanging bulk water protons. Although increasing the exchange rate of the bound protons enhances the CEST effect, this also causes exchange broadening and increases the B(1) required for saturation. For a given B(1), there is an optimal exchange rate that results in a maximal CEST effect. This numerical approach, which was formulated for a three-pool case, was incorporated into a MATLAB nonlinear least-square optimization routine, and the results were in excellent agreement with experimental Z-spectra obtained with an aqueous solution of a paramagnetic CEST agent containing two different types of bound protons (bound water and amide protons).
347 citations
••
259 citations
••
TL;DR: Protonation of the noncoordinating phosphonate groups appears to catalyze prototropic exchange of the bound water protons, thereby providing a mechanism for enhanced water contrast below pH 7.
Abstract: A tetrasubstituted derivative of 1,4,7,10-tetraazacyclododecane with amide coordinating groups and extended noncoordinating phosphonate groups forms a complex with gadolinium(III) (shown in the picture) which contains one slowly exchanging inner-sphere water molecule (τM=21 μs). The 20-MHz water proton relaxivity of the complex was found to be highly pH dependent. Protonation of the noncoordinating phosphonate groups appears to catalyze prototropic exchange of the bound water protons, thereby providing a mechanism for enhanced water contrast below pH 7.
247 citations
••
TL;DR: The europium(III) complex of a DOTA-tetraamide ligand containing two phenyl boronate pendent arms binds glucose reversibly and offers the possibility of high-sensitivity MR imaging glucose in tissues using bulk water protons as antenna.
Abstract: The europium(III) complex of a DOTA-tetraamide ligand (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N' ',N' ''-tetraacetic acids) containing two phenyl boronate pendent arms binds glucose reversibly with an association constant of 383 M-1 at pH 7. Glucose binding results in slowing of water exchange between a single Eu(III)-bound water molecule and bulk water, and this can be imaged by MRI using chemical exchange saturation transfer (CEST) imaging sequence. This metabolite-responsive paramagnetic CEST agent responds to changes in glucose over the physiologically important range (0-20 mM), and thus it offers the possibility of high-sensitivity MR imaging glucose in tissues using bulk water protons as antenna.
182 citations
••
TL;DR: An inverse relationship between pHe and tumor perfusion is revealed and new MRI methods based on pH‐sensitive T1 relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution.
Abstract: Previous studies using MR spectroscopy have shown that the extracellular pH (pHe) of tumors is acidic compared to normal tissues. This has a number of important sequelae that favor the emergence of more aggressive and therapy-resistant tumors. New MRI methods based on pH-sensitive T1 relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH-dependent GdDOTA-4AmP 5- and a pH-independent analog, GdDOTP 5- , were used to image renal pH in mice. The current study has used a similar approach to image pHe in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP 5- was found to be affected by the higher extracellular protein content of tumors. Second, the pixel-by-pixel analysis of the GdDOTP 5- and GdDOTA-4AmP 5- pharmacokinetics showed significant dispersion, likely due to the temporal fluctuations in tumor perfusion. However, there was a robust correlation between the maximal enhancements produced by the two boluses. Therefore, to account for the local time-courses differences, pHe maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pHe and the time to maximal intensity maps revealed an inverse relationship between pHe and tumor perfusion. Magn Reson Med 55:309 –315, 2006.
158 citations
Cited by
More filters
••
TL;DR: The ability of employing zeta potential to target drug delivery systems to, and drug release at specific sites of the body are discussed.
Abstract: The zeta potential (ZP) of colloidal systems and nano-medicines, as well as their particle size exert a major effect on the various properties of nano-drug delivery systems. Not only the stability of dosage forms and their release rate are affected but also their circulation in the blood stream and absorption into body membranes are dramatically altered by ZP. In this paper the effect of ZP on the various properties of nano-medicines are reviewed. Furthermore, the ability of employing zeta potential to target drug delivery systems to, and drug release at specific sites of the body are discussed.
1,276 citations
••
TL;DR: A sensitive and selective method for glucose detection was developed using glucose oxidase (GOx) and the as-prepared Fe(3)O(4) MNPs and showed great potential applications in varieties of simple, robust, and easy-to-make analytical approaches in the future.
Abstract: Artificial enzyme mimetics are a current research interest because natural enzymes bear some serious disadvantages, such as their catalytic activity can be easily inhibited and they can be digested by proteases A very recently study reported by Yan et al has proven that Fe3O4 magnetic nanoparticles (MNPs) exhibit an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, though MNPs are usually thought to be biological and chemical inert (Gao, L Z; Zhuang, J; Nie, L; Zhang, J B; Zhang, Y; Gu, N; Wang, T H; Feng, J; Yang, D L; Perrett, S; Yan, X Y Nat Nanotechnol 2007, 2, 577−583) In the present work, we just make use of the novel properties of Fe3O4 MNPs as peroxidase mimetics reported by Yan et al to detect H2O2 The Fe3O4 MNPs were prepared via a coprecipitation method The as-prepared Fe3O4 MNPs were then used to catalyze the oxidation of a peroxidase substrate 2,2‘-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) by H2O2 to the oxi
1,230 citations
••
TL;DR: CO2 from the pentose phosphate pathway is an alternative source of acidity, showing that hypoxia and extracellular acidity are, while being independent from each other, deeply associated with the cellular microenvironment.
Abstract: Acidic extracellular pH is a major feature of tumor tissue, extracellular acidification being primarily considered to be due to lactate secretion from anaerobic glycolysis. Clinicopathological evidence shows that transporters and pumps contribute to H+ secretion, such as the Na+/H+ exchanger, the H+-lactate co-transporter, monocarboxylate transporters, and the proton pump (H+-ATPase); these may also be associated with tumor metastasis. An acidic extracellular pH not only activates secreted lysosomal enzymes that have an optimal pH in the acidic range, but induces the expression of certain genes of pro-metastatic factors through an intracellular signaling cascade that is different from hypoxia. In addition to lactate, CO2 from the pentose phosphate pathway is an alternative source of acidity, showing that hypoxia and extracellular acidity are, while being independent from each other, deeply associated with the cellular microenvironment. In this article, the importance of an acidic extracellular pH as a microenvironmental factor participating in tumor progression is reviewed.
1,000 citations
••
TL;DR: P pH effects were noninvasively imaged in ischemic rat brain to show the potential of amide proton transfer (APT) contrast for detecting acute stroke, and opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, in clinical imaging.
Abstract: In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.
973 citations
••
University of Marburg1, University of Erlangen-Nuremberg2, Rovira i Virgili University3, Max Planck Society4, University of Göttingen5, University of California, Los Angeles6, International School for Advanced Studies7, University of Melbourne8, University of Trieste9, Ikerbasque10, University of Toronto11, Nanyang Technological University12, National Institutes of Health13, Stanford University14, Shanghai Jiao Tong University15, Tongji University16, University of Seville17, Karolinska Institutet18, Drexel University19, Sichuan University20, Rice University21, Northwestern University22, University of Basel23, Zhejiang University24, Heidelberg University25, University of Tokyo26, Harvard University27, University of Utah28, University of Michigan29, Swiss Federal Laboratories for Materials Science and Technology30, Seoul National University31, Saarland University32, Columbia University33, Chinese Academy of Sciences34, Kazan Federal University35, Emory University36, University of California, Irvine37, Autonomous University of Barcelona38, University of Massachusetts Amherst39, Pennsylvania State University40, Ghent University41, Imperial College London42, National Tsing Hua University43, South China University of Technology44, University of Ulm45, Hebrew University of Jerusalem46, Huazhong University of Science and Technology47, Peking University48
TL;DR: An overview of recent developments in nanomedicine is provided and the current challenges and upcoming opportunities for the field are highlighted and translation to the clinic is highlighted.
Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
926 citations