Preparation and characterization of paramagnetic polychelates and their protein conjugates.
TL;DR: The gadolinium complexes of poly-L-lysine-poly and poly-4,7,10-tetraazacyclodododecane and their conjugates with human serum albumin (HSA) have been prepared and characterized and the molar relaxities were 2-3-fold higher than those of the corresponding monomeric metal complexes.
About: This article is published in Bioconjugate Chemistry.The article was published on 1990-01-01. It has received 108 citations till now. The article focuses on the topics: DOTA.
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TL;DR: A. Relaxivity 2331 E. Outerand Second-Sphere relaxivity 2334 F. Methods of Improving Relaxivity 2336 V. Macromolecular Conjugates 2336.
Abstract: A. Water Exchange 2326 B. Proton Exchange 2327 C. Electronic Relaxation 2327 D. Relaxivity 2331 E. Outerand Second-Sphere Relaxivity 2334 F. Methods of Improving Relaxivity 2336 V. Macromolecular Conjugates 2336 A. Introduction 2336 B. General Conjugation Methods 2336 C. Synthetic Linear Polymers 2336 D. Synthetic Dendrimer-Based Agents 2338 E. Naturally Occurring Polymers (Proteins, Polysaccharides, and Nucleic Acids) 2339
4,125 citations
TL;DR: It is observed that these dendrimer‐based agents enhance conventional MR images and 3D time of flight MR angiograms, and that those with molecular weights of 8,508 and 139,000 g/mole have enhancement half lives of 40 ± 10 and 200 ± 100 min, much longer than the 24 ± 4 min measured for Gd(III)‐diethylenetriaminepentaacetic acid.
Abstract: We have developed a new class of magnetic resonance imaging contrast agents with large proton relaxation enhancements and high molecular relaxivities. The reagents are built from the polyamidoamine form of Starburst dendrimers in which free amines have been conjugated to the chelator 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid. The dendrimer gadolinium poly-chelates have enhancement factors, i.e., the ratio of the relaxivity per Gd(III) ion to that of Gd(III)-diethylenetriaminepentaacetic acid, of up to 6. These factors are more than twice those observed for analogous metal-chelate conjugates formed with serum albumins, polylysine, or dextran. One of the dendrimer-metal chelate conjugates has 170 gadolinium ions bound, which greatly exceeds the number bound to other macromolecular agents reported in the literature, and has a molecular relaxivity of 5,800 (mM.s)-1, at 25 MHz, 20 degrees C, and pH of 7.4. We observed that these dendrimer-based agents enhance conventional MR images and 3D time of flight MR angiograms, and that those with molecular weights of 8,508 and 139,000 g/mole have enhancement half lives of 40 +/- 10 and 200 +/- 100 min, much longer than the 24 +/- 4 min measured for Gd(III)-diethylenetriaminepentaacetic acid. Our results suggest that this new and powerful class of contrast agents have the potential for diverse and extensive application in MR imaging.
709 citations
TL;DR: In this review, small molecule agents are introduced, but focus primarily on macromolecular MR contrast agents, particularly those containing gadolinium (Gd 3+ ) that are assembled or based in part on these same small molecules.
Abstract: Magnetism in medicine has had a long and interesting history In the 10 th century AD, Egyptian physician and philosopher Avicenna prescribed a grain of magnetite dissolved in milk for the accidental swallowing of rust reasoning that magnetite would render the poisonous iron inert by attracting it and accelerating its excretion through the intestine1 A thousand years later on July 3, 1977, “Indomitable”, the little machine that could, labored for five hours to produce one image, an event that used magnetism to change the landscape of modern medicine 2 Looking at the homemade superconducting magnet constructed from 30 miles of niobiumtitanium wire that now resides in its rightful place at the Smithsonian Institution, it is incredible to comprehend how in a mere 30 years magnetic resonance imaging (MRI) has gone from its crude, almost ugly, human scan to where physicians can now regularly order MRIs off their menu of diagnostic tools because of its exquisite anatomical resolution, routinely down to 05 to 1 mm When the field was first reviewed in this journal in 1987, 3 only 39 papers were found in Medline with keywords “gado-“ and “MRI” 4 Today, this same search on PubMed pulls out over 250,000 records, of which a significant component has been development of MR contrast agents The human body is essentially a super-sized water bottle, with about two-thirds of its weight consisting of water Water's hydrogen atoms are able to act as microscopic compass needles that stand “at attention” when placed in a strong magnetic field When submitted to pulses of radio waves, their magnetic alignment is disrupted and the differences in how they relax to the previous state are used to generate images Contrast agents can act to catalyze the process of the return to the ground relaxed state Now commonplace in the clinic, paramagnetic or superparamagnetic metal ions are administered in 40–50% of the 7–10 million MR examinations per year 5 These image-enhancing contrast agents add significant morphological and functional information to unenhanced MR images, allowing for enhanced tissue contrast, characterization of lesions, and evaluation of perfusion and flow-related abnormalities In this review, we will introduce small molecule agents, but focus primarily on macromolecular MR contrast agents, particularly those containing gadolinium (Gd 3+ ) that are assembled or based in part on these same small molecules A brief discussion on iron oxide and manganese (Mn 2+ ) agents is also provided
568 citations
TL;DR: Classification includes composition, magnetic properties, biodistribution and imaging applications, which covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific.
Abstract: A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.
506 citations
Cites background from "Preparation and characterization of..."
...(50) have synthesized a poly-(L-lysine) containing 60–90 chelating groups (DTPA or DOTA)....
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454 citations
References
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1,900 citations
TL;DR: A study of the specificity of the reaction indicates that it occurs only with the S − group (actual or potential, as in thiourea), and heavy-metal ions interfere with the reaction by irreversibly bonding any S − ions.
1,053 citations
TL;DR: A simple and efficient method of covalently coupling the strong chelator diethylenetriaminepentaacetic acid to proteins was developed for radiolabeling immunoglobulin G antibodies.
Abstract: A simple and efficient method of covalently coupling the strong chelator diethylenetriaminepentaacetic acid to proteins was developed for radiolabeling immunoglobulin G antibodies. After being coupled and labeled with indium-111, a monoclonal antibody to carcinoembryonic antigen retained its ability to bind to its antigen in vitro and in vivo. In nude mice with a human colorectal xenograft, 41 percent of the injected radioactivity became localized in each gram of xenograft at 24 hours compared with 9 percent for control antibody and 19 percent for radioiodinated antibody to carcinoembryonic antigen.
451 citations
TL;DR: The labeled products retain their immunoreactivity, as illustrated by experiments in vivo with chelate-conjugated antibody to mouse I-AK antigen.
406 citations
TL;DR: A simple procedure for covalently coupling diethylenetriaminepentaacetic acid to proteins and creates hexadentate chelating sites for metal ions on proteins is described.
379 citations