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Design And Evaluation Of Gadoliniumiii Complexes As High Relaxivity Mri Contrast Agents
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Book Synopsis Design and Evaluation of Gadolinium(III) Complexes as High-relaxivity MRI Contrast Agents by : Eric Joseph Werner
Download or read book Design and Evaluation of Gadolinium(III) Complexes as High-relaxivity MRI Contrast Agents written by Eric Joseph Werner and published by . This book was released on 2007 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: The emergence of new instrumentation and applications for Magnetic Resonance Imaging (MRI) invites the development of more efficient contrast agents. Current commercial agents employ gadolinium(III) complexes of polyaminocarboxylate ligands and achieve modest relaxivities (increase in water proton longitudinal relaxation) due to a low number of coordinated water molecules (q = 1) and slow water exchange rates. Raymond and coworkers (University of California, Berkeley) have developed a family of stable hydroxypyridinone (HOPO)-based Gd(III) chelates that show promise as next-generation contrast agents due to an increased hydration number and faster water exchange rates leading to relaxivities that are about twice the values for commercial agents. A unique aspect of these compounds is that, unlike what is observed for currently used clinical agents, the relaxivity does not typically decrease with increasing magnetic field strength (e.g. 3 T).
Book Synopsis High Relaxivity Polymeric MRI Contrast Agents by : Thomas Berki
Download or read book High Relaxivity Polymeric MRI Contrast Agents written by Thomas Berki and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging by : Andre S. Merbach
Download or read book The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging written by Andre S. Merbach and published by John Wiley & Sons. This book was released on 2013-02-19 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Resonance Imaging (MRI) is one of the most important tools in clinical diagnostics and biomedical research. The number of MRI scanners operating around the world is estimated to be approximately 20,000, and the development of contrast agents, currently used in about a third of the 50 million clinical MRI examinations performed every year, has largely contributed to this significant achievement. This completely revised and extended second edition: Includes new chapters on targeted, responsive, PARACEST and nanoparticle MRI contrast agents. Covers the basic chemistries, MR physics and the most important techniques used by chemists in the characterization of MRI agents from every angle from synthesis to safety considerations. Is written for all of those involved in the development and application of contrast agents in MRI. Presented in colour, it provides readers with true representation and easy interpretation of the images. A word from the Authors: Twelve years after the first edition published, we are convinced that the chemistry of MRI agents has a bright future. By assembling all important information on the design principles and functioning of magnetic resonance imaging probes, this book intends to be a useful tool for both experts and newcomers in the field. We hope that it helps inspire further work in order to create more efficient and specific imaging probes that will allow materializing the dream of seeing even deeper and better inside the living organisms. Reviews of the First Edition: "...attempts, for the first time, to review the whole spectrum of involved chemical disciplines in this technique..."—Journal of the American Chemical Society "...well balanced in its scope and attention to detail...a valuable addition to the library of MR scientists..."—NMR in Biomedicine
Book Synopsis Contrast Agents I by : Werner Krause
Download or read book Contrast Agents I written by Werner Krause and published by Springer. This book was released on 2003-07-01 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extracellular MRI and X-ray contrast agents are characterized by their phar- cokinetic behaviour.After intravascular injection their plasma-level time curve is characeterized by two phases. The agents are rapidly distributed between plasma and interstitial spaces followed by renal elimination with a terminal half-live of approximatly 1–2 hours. They are excreted via the kidneys in unchanged form by glomerular filtration. Extracellular water-soluble contrast agents to be applied for X-ray imaging were introduced into clinical practice in 1923. Since that time they have proved to be most valuable tools in diagnostics.They contain iodine as the element of choice with a sufficiently high atomic weight difference to organic tissue. As positive contrast agents their attenuation of radiation is higher compared with the attenuation of the surrounding tissue. By this contrast enhancement X-ray diagnostics could be improved dramatically. In 2,4,6-triiodobenzoic acid derivatives iodine is firmly bound. Nowadays diamides of the 2,4,6-triiodo-5-acylamino-isophthalic acid like iopromide (Ultravist, Fig. 1) are used as non-ionic (neutral) X-ray contrast agents in most cases [1].
Book Synopsis Contrast Agents for MRI by : Valérie C Pierre
Download or read book Contrast Agents for MRI written by Valérie C Pierre and published by Royal Society of Chemistry. This book was released on 2017-11-09 with total page 612 pages. Available in PDF, EPUB and Kindle. Book excerpt: As a practical reference guide for designing and performing experiments, this book focuses on the five most common classes of contrast agents for MRI namely gadolinium complexes, chemical exchange saturation transfer agents, iron oxide nanoparticles, manganese complexes and fluorine contrast agents. It describes how to characterize and evaluate them and for each class, a description of the theory behind their mechanisms is discussed briefly to orient the new reader. Detailed subchapters discuss the different physical chemistry methods used to characterize them in terms of their efficacy, safety and in vivo behavior. Important consideration is also given to the different physical properties that affect the performance of the contrast agents. The editors and contributors are at the forefront of research in the field of MRI contrast agents and this unique, cutting edge book is a timely addition to the literature in this area.
Book Synopsis High-Relaxivity MRI Contrast Agents by :
Download or read book High-Relaxivity MRI Contrast Agents written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.
Download or read book MRI written by Brian M. Dale and published by John Wiley & Sons. This book was released on 2015-08-06 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fifth edition of the most accessible introduction to MRI principles and applications from renowned teachers in the field provides an understandable yet comprehensive update. Accessible introductory guide from renowned teachers in the field Provides a concise yet thorough introduction for MRI focusing on fundamental physics, pulse sequences, and clinical applications without presenting advanced math Takes a practical approach, including up-to-date protocols, and supports technical concepts with thorough explanations and illustrations Highlights sections that are directly relevant to radiology board exams Presents new information on the latest scan techniques and applications including 3 Tesla whole body scanners, safety issues, and the nephrotoxic effects of gadolinium-based contrast media
Book Synopsis Rare Earth Coordination Chemistry by : Chun-Hui Huang
Download or read book Rare Earth Coordination Chemistry written by Chun-Hui Huang and published by John Wiley & Sons. This book was released on 2011-09-23 with total page 602 pages. Available in PDF, EPUB and Kindle. Book excerpt: Edited by a highly regarded scientist and with contributions from sixteen international research groups, spanning Asia and North America, Rare Earth Coordination Chemistry: Fundamentals and Applications provides the first one-stop reference resource for important accomplishments in the area of rare earth. Consisting of two parts, Fundamentals and Applications, readers are armed with the systematic basic aspects of rare earth coordination chemistry and presented with the latest developments in the applications of rare earths. The systematic introduction of basic knowledge, application technology and the latest developments in the field, makes this ideal for readers across both introductory and specialist levels.
Book Synopsis MRI Contrast Agents by : Sophie Laurent
Download or read book MRI Contrast Agents written by Sophie Laurent and published by Springer. This book was released on 2016-11-03 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the multiple aspects of (i) preparation of the magnetic core, (ii) the stabilization with different coatings, (iii) the physico-chemical characterization and (iv) the vectorization to obtain specific nanosystems. Several bio-applications are also presented in this book. In the early days of Magnetic Resonance Imaging (MRI), paramagnetic ions were proposed as contrast agents to enhance the diagnostic quality of MR images. Since then, academic and industrial efforts have been devoted to the development of new and more efficient molecular, supramolecular and nanoparticular systems. Old concepts and theories, like paramagnetic relaxation, were revisited and exploited, leading to new scientific tracks. With their high relaxivity payload, the superparamagnetic nanoparticles are very appealing in the context of molecular imaging but challenges are still numerous: absence of toxicity, specificity, ability to cross the biological barriers, etc.
Book Synopsis Ligand Design in Medicinal Inorganic Chemistry by : Tim Storr
Download or read book Ligand Design in Medicinal Inorganic Chemistry written by Tim Storr and published by John Wiley & Sons. This book was released on 2014-06-12 with total page 650 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Ligand Design in Medicinal Inorganic Chemistry presents the state-of-the-art in ligand design for medicinal inorganic chemistry applications. Each individual chapter describes and explores the application of compounds that either target a disease site, or are activated by a disease-specific biological process. Ligand design is discussed in the following areas: Platinum, Ruthenium, and Gold-containing anticancer agents Emissive metal-based optical probes Metal-based antimalarial agents Metal overload disorders Modulation of metal-protein interactions in neurodegenerative diseases Photoactivatable metal complexes and their use in biology and medicine Radiodiagnostic agents and Magnetic Resonance Imaging (MRI) agents Carbohydrate-containing ligands and Schiff-base ligands in Medicinal Inorganic Chemistry Metalloprotein inhibitors Ligand Design in Medicinal Inorganic Chemistry provides graduate students, industrial chemists and academic researchers with a launching pad for new research in medicinal chemistry.
Book Synopsis Lanthanide Complexes for Magnetic Resonance Imaging (MRI) Contrast Agents and Luminescent Sensors by : Cong Li
Download or read book Lanthanide Complexes for Magnetic Resonance Imaging (MRI) Contrast Agents and Luminescent Sensors written by Cong Li and published by . This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Lanthanide Complexes for Magnetic Resonance Imaging (MRI) Contrast Agents and Luminescent Sensors" by Cong, Li, 李聰, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled LANTHANIDE COMPLEXES FOR MAGNETIC RESONANCE IMAGING (MRI) CONTRAST AGENTS AND LUMINESCENT SENSORS Submitted by Li Cong for the degree of Doctor of Philosophy at The University of Hong Kong in June 2004 Magnetic resonance imaging (MRI) and bioluminescence imaging are widely used in medical diagnosis. There is a need to develop MRI contrast agents and 3+ 3+ luminescence sensors with higher sensitivity and specificity. Novel Gd and Tb complexes endowed with different functionalities have been synthesized and studied. In this work, a series of general and straightforward methods for the preparation of mono, 1,4 bis and tris N-alkylation of cyclen in high yields and with unprecedented regioselectivity were developed. These protocols are useful in introducing different functional groups to the 1,4,7,10-tetraazacyclododecane (cyclen) in a single step without the use of unnecessary protecting groups. For example, the functionalised 1,4,7-tris-(acetic acid)-1,4,7,10-tetraazacyclododecane (DO3A) derivatives that used to be prepared by multiple steps can now be achieved in two simple steps with attractive features such as high yield, operational convenience and cost economy. 3+ The novel mononuclear Gd polyaminocarboxylates based on cyclen, GdL1- GdL7, were synthesized. Functional groups, such as crown ethers with different ring sizes, β-D-glucopyranose, guanidinium and quinine alkylated diaza-18C6, were introduced into these complexes to achieve target-specificity. The synthesis, structural 1 13 characterization measured by single crystal X-ray analysis, H and C NMR, ESI-MS, HRFAB-MS and elemental analysis, luminescence-lifetime measurements, the relaxometric investigations of the complexes by nuclear magnetic resonance 17 dispersion (NMRD) profiles, variable-temperature O NMR transverse relaxation and pH dependence relaxivity, in vivo MRI studies and in vitro toxicity studies were 3+ discussed. Relaxivities of the four Gd complexes, GdL1, GdL3, GdL5 and GdL6 -1 -1 -1 -1 are in the descending order of GdL1 (9.65 mM s ) >GdL3 (9.36 mM s ) >GdL6 -1 -1 -1 -1 (7.34 mM s ) > GdL5 (3.75 mM s ) measured at 20 MHz and 25C. Compared to -1 -1 the commercially available contrast agents [Gd(DOTA)(H O)] (4.74 mM s ) and -1 -1 [Gd(DO3A)(H O) ] (5.72 mM s ) with two bound water molecules, GdL1, GdL3 2 2 and GdL6 showed much higher relaxivity. The most striking result is the water molecule exchange lifetime of GdL1, which was measured as 55 ns, very close to the optimum value of 20-30 ns in theory. GdL1, GdL3 and GdL6 also demonstrated outstanding performances in the MRI studies based on small animals. The maximal renal and hepatic intensity enhancements (IE) induced by GdL1 were 200% and 105% respectively above the control level, and much higher than those of Gd-DOTA at 123% and 70%. Moreover, GdL1 and GdL3 afforded much longer resident lifetimes in the kidney cortex and liver parenchyma. It is noteworthy that GdL1 showed obvious target-specificity to liver tissue. The maximal hepatic IE induced by GdL1 with low dosage (90%, 0.03 mmol/kg) is even higher than that of Gd-DOTA with three times dosage (70%, 0.1 mmol/kg). Furthermore, an in vitro MTT assay confirmed that the cytotoxicity of GdL1 is quite low even at high concentration (10 mM). The luminescent properties of TbL1, TbL3 and TbL7 were investigated in aqueous solution. TbL
Book Synopsis The Design, Syntheses, and Physico-chemical Studies of MRI Contrast Agents by : Alan Kazunari Marumoto
Download or read book The Design, Syntheses, and Physico-chemical Studies of MRI Contrast Agents written by Alan Kazunari Marumoto and published by . This book was released on 1994 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Resonance Imaging (MRI) is a popular and powerful clinical diagnostic tool. The development of MRI contrast agents allows for even greater diagnostic ability. This thesis will address the design, syntheses and physico-chemical studies of two specific classes of MRI contrast agents: the DTPA bisamide macrocycles and the bile salt-like hepatobiliary targeted contrast agents. The DTPA bisamide macrocycles are synthesized from the condensation product of DTPA biscyclic-dianhydride with an appropriate 1,N-diaminoalkane. Physical properties such as metal binding and albumin binding as well as imaging studies, demonstrated that small DTPA bisamide macrocycles (15-18 member macrocycles) do not bind Gd(3+) as strongly as the linear DTPA derivatives. In addition, imaging studies demonstrated breast tumor and kidney enhancement. Nuclear Magnetic Resonance Dispersions (NMRD) were measured in hypotonic, isotonic, and hypertonic solutions with and without albumin present. The results of the NMRD coupled with the albumin binding studies indicate that the albumin associated Gd(3+)-complexes have higher relaxivity than the unbound Gd(3+) monochelates. This property appears to be weakly correlated with the lipophilicity of the chelates. The second class of contrast agents attempts to exploit the anion uptake receptors in the liver as a means of targeting agents to the liver and biliary tract. These compounds are synthesized from cholic acid derivatives. The cholic acid derivatives are modified to have a free primary amine. A DTPA chelate is attached to the free amide via an amide bond to form the bile-salt like contrast agents. MR imaging with these agents demonstrated liver enhancement in rats.
Book Synopsis High Relaxivity Biomolecule Based Contrast Agents Engineered for Molecular Functional Magnetic Resonance Imaging by : Vivian Hsieh (Ph. D.)
Download or read book High Relaxivity Biomolecule Based Contrast Agents Engineered for Molecular Functional Magnetic Resonance Imaging written by Vivian Hsieh (Ph. D.) and published by . This book was released on 2016 with total page 93 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic resonance imaging (MRI) is a powerful neuroimaging tool that allows non-invasive visualization of the brain with high spatial and temporal resolution. Research on MRI contrast agents and their application to problems in neuroscience is burgeoning, and there is particular interest in developing MRI agents that are sensitive to time varying components of neurophysiology. Relatively recent advances in biomolecular probes has demonstrated the potential and versatility of bioengineered MRI sensors for molecular imaging. However, a major limitation of these probes is the high concentration needed for imaging, which can lead to issues such as analyte buffering and toxicity, and restrict the applicability of the sensors. In this work, we explore two approaches for developing high relaxivity protein-based contrast agents to address the issues of low detectability. First, we coupled monoamine sensing with the disaggregation of superparamagnetic iron oxide nanoparticles (SPIOs). Ligand detection was imparted by integration of a monoamine sensing protein-based contrast agent derived from P450- BM3h (BM3). We demonstrated that this mechanism can produce robust signal changes of approximately 2-fold, while reducing the concentration of BM3 needed by 100-fold compared to the amount needed when only the protein is used for imaging. The second method demonstrated the feasibility of using semi-rational protein design to engineer a high relaxivity metalloprotein by tuning phenylalanine hydroxylase to bind gadolinium at high affinity. Mutations were found that increased the protein affinity by two orders of magnitude and enhanced relaxivity. The results of this thesis advance approaches for creating high relaxivity contrast agents which can be applied to the development of probes for other analytes, ultimately advancing and broadening the applicability of bioengineered probes in molecular functional neuroimaging.
Book Synopsis New Ligands for Lanthanides and Transition Metals Toward Magnetic Resonance Imaging Contrast Agents by : Melissa M. Lewis
Download or read book New Ligands for Lanthanides and Transition Metals Toward Magnetic Resonance Imaging Contrast Agents written by Melissa M. Lewis and published by . This book was released on 2014 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Resonance Imaging (MRI) is a non-invasive technique used in medical imaging with applications in diagnosis, stage determination and monitoring of the progress of disease. Although contrast agents have been used to enhance the image generated by MRI, it still suffers the major shortcoming of low sensitivity. This has led to a thrust to develop contrast agents that improve the sensitivity by relaxation (T1 and T2) as well as by chemical exchange saturation transfer (CEST). To further aid in the development of sensitive MRI contrast agents, the synthesis and evaluation of lanthanide and transition metal complexes was executed. The results are presented herein. Chapter 2 investigated pH dependent reversible binding on CEST effect and relaxivity in macrocyclic complexes possessing three of the same arms and a lone p-nitrophenol arm. Unfortunately, only the Tb3+complex had a small CEST signal. T1 relaxivity of the Gd3+ complex showed high relaxivity at acidic pH and low relaxivity at basic pH. Chapter 3 discussed the rigidification of the DOTAM structure as a means to promote the formation of the SAP isomer for CEST signal generation. These ligands were rigidified by at least one cyclohexyl group and were found to be very selective toward transition metals over lanthanides. However, none of the complexes investigated generated a CEST signal. Chapter 4 attempted to examine the amide CEST signal of DOTAM-tetraanilide complexes containing various para-substituents that would limit T2 exchange and increase amide-based pH measurements. Due to the insolubility of the other complexes, only the p-H and p-OMe complexes were evaluated. The CEST spectrum of the Tm3+-p-OMe complex revealed two amide signals. The absence of a bound water molecule in the Tm3+ agents allowed for higher signal to noise ratios because of reduced T1 and T2 relaxation. Chapter 5 involved a model study that assessed the electronic effects of para-substituents on the amide CEST signal and relaxivity of DO3A-monoanilide complexes. CEST spectra of only the Tm3+complexes could be acquired. The various substituents allowed a CEST effect to be observed at different pH values. The T1 relaxivities of the Dy3+ and Tm3+ complexes were both low, while the Dy3+ complexes had much higher T2 relaxivities as compared to the Tm3+-based ones. Finally, Chapter 6 highlighted the attempt to synthesize para-phosphonate monoanilide analogues of the DOTAM tetraanilide complexes mentioned in Chapter 4, which would be suitable for in vivo studies. It is anticipated that the two amide signals seen in the CEST spectrum of the Tm3+-p-OMe complex would still persist in the modified complex, thus providing a means of a concentration independent ratiometric analysis of the CEST effect. Due to synthetic challenges, the synthesis of these modified complexes is still ongoing.
Book Synopsis Molecular and Cellular MR Imaging by : Michel M.J. Modo
Download or read book Molecular and Cellular MR Imaging written by Michel M.J. Modo and published by CRC Press. This book was released on 2007-03-28 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ability of molecular and cellular imaging to track the survival, migration, and differentiation of cells in vivo as well as monitor particular gene expression in living subjects is rapidly moving from the research laboratory into daily clinical settings. The interdisciplinary nature of the field mandates a constant dialogue among molecular and
Book Synopsis Next Generation Magnetic Resonance Imaging Contrast Agents by : Piper Julia Klemm
Download or read book Next Generation Magnetic Resonance Imaging Contrast Agents written by Piper Julia Klemm and published by . This book was released on 2012 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic resonance imaging (MRI) is one of the most powerful diagnostic techniques at the disposal of the medical community. Its success in the clinic, with 75 to 90 million scans performed worldwide annually, can be attributed in part to the use of injectable contrast agents to improve signal differentiation between healthy and pathological tissue. These contrast agents primarily use Gd(III) as the paramagnetic metal ion to induce contrast. With seven unpaired electrons, Gd(III) has the most paramagnetic character of any nonradioactive element. Aqueous Gd(III), however, is highly toxic; hence contrast agents use chelators to encapsulate the Gd(III) ion, which protects the patient from from the Gd(III) ion. While these chelators are necessary, they greatly decrease the relaxivity of the current commercial contrast agents. Commercial contrast agents are similar in that they are heteroatom chelators (N, O) and octadentate coordination, leaving only one open site for water coordination. Additionally, given their steric bulk, the water exchange mechanism with bulk solvent is a laboriously hindered dissociative mechanism. These factors contribute to the low efficiency of these Gd(III) complexes, as measured in relaxivity. Diagnostic scans typically inject 8-10 g of these complexes to achieve sufficient signal. Hydroxypyridinone (HOPO) chelators have emerged as a superior alternative to current commercial compounds. Using a tris(2-aminoethyl)amine (TREN) capping moiety, three bidentate HOPO chelators form a hexadentate ligand. These TREN-tris-HOPO ligands leave multiple open sites for water coordination and exhibit rapid water exchange with bulk solvent, due to their reduced steric bulk and associative exchange mechanism. These ligands use all-oxygen-donor chelators, capitalizing on the oxophilicity of Gd(III) to form highly stable complexes. From this superior family of chelators, a variety of approaches can be used to develop the next generation of MRI contrast agents. Increasing molecular weight and tumbling time has been a strategy for increasing relaxivity and efficiency of MRI contrast agents. Through macromolecular conjugation, relaxivity is readily increased; simultaneously, these macromolecules provide the potential for building multimodal and multifunctional diagnostic and therapeutic agents. The potential applications for this class of materials are further increased with the addition of targeting functionality. These agents must have the ability to be fully and rapidly excreted and have facile and uniform large-scale syntheses to be candidates for the clinic. The esteramide (EA) dendrimer is one such macromolecular platform. With eight sites for contrast agent conjugation, the esteramide dendrimer readily loads many distinct HOPO ligands with multiple lanthanides for multimodal imaging. With close to 40 kDa of polyethylene glycol units, the Gd-HOPO-EA macromolecular architecture is highly soluble and biocompatible. Furthermore, the ester core of the dendrimer is degradable under in vivo conditions, easing renal clearance with four smaller moieties. The superior properties of this system inspired investigation into a variety of other macromolecular systems. Porous silica mesoparticles provide a rigid architecture that is much larger than other macromolecules evaluated and can hold greater than 108 small molecule MRI contrast complexes. The surfaces of these particles are readily functionalized and suitable for conjugation with most small molecule MRI contrast agents. These structures use a nontoxic silica infrastructure and are excreted renally despite their large size, making them viable candidates for further in vitro and in vivo study. Gold nanoparticles (AuNP) as a solid-support system have the most potential for use as multifunctional diagnostic and therapeutic compounds. AuNP have been long used for enhancing computed tomography (CT) imaging and have recently emerged as a cancer therapeutic when their structure is irradiated. These compounds are readily synthesized in large scales and have loading sites that are close together to hold multi-tethered Gadolinium-HOPO systems for multifunctional imaging. Using a variety of macromolecules to capitalize on the structural relationship between relaxivity and size, per-Gd and per-macromolecule-Gd relaxivity have been increased dramatically at clinically and physiologically relevant conditions. These improvements show that the combination of carefully designed macromolecules with excellent HOPO chelators produces an ideal MRI contrast agent for the clinic of the future.
Book Synopsis Metallo-Drugs: Development and Action of Anticancer Agents by : Astrid Sigel
Download or read book Metallo-Drugs: Development and Action of Anticancer Agents written by Astrid Sigel and published by Walter de Gruyter GmbH & Co KG. This book was released on 2018-02-05 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.
