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Journal ArticleDOI

Triaza-based amphiphilic chelators: Synthetic route, in vitro characterization and in vivo studies of their Ga(III) and Al(III) chelates

TL;DR: The synthesis and in vitro and in vivo studies of a series of micelles-forming Ga(III) chelates targeted for the liver are described, showing higher liver uptake for [(67)Ga](NOTAC8) in comparison to [(67]Ga]( NOTAC6), consistent with a longer alpha-alkyl chain and a higher lipophilicity.
About: This article is published in Journal of Inorganic Biochemistry.The article was published on 2010-10-01 and is currently open access. It has received 25 citations till now. The article focuses on the topics: Blood serum.
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Journal ArticleDOI
TL;DR: The future development of the 68Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of 68Ga, automation of the radiopharm pharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies.
Abstract: Positron Emission Tomography (PET) experienced accelerated development and has become an established method for medical research and clinical routine diagnostics on patient individualized basis. Development and availability of new radiopharmaceuticals specific for particular diseases is one of the driving forces of the expansion of clinical PET. The future development of the ⁶⁸Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of ⁶⁸Ga, automation of the radiopharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies for improved quantitation accuracy, PET radiopharmaceutical regulations as well as advances in radiopharmaceutical chemistry. The review presents the prospects of the ⁶⁸Ga-based radiopharmaceutical development on the basis of the current status of these aspects as well as wide range and variety of imaging agents.

259 citations


Cites background from "Triaza-based amphiphilic chelators:..."

  • ...Micelle agents were formed by the aggregation of amphiphilic ligands comprising NOTA or DOTA coupled to an α-alkyl chain via acetate pendant arms [304, 305]....

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Journal ArticleDOI
TL;DR: The results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.

133 citations

Journal ArticleDOI
TL;DR: Complex formation studies in acidic solutions indicate that Ga(3+) complexes of the phosphinate ligands are formed quickly (minutes) and quantitatively even at pH <2.5, and the discussed TRAP ligANDs are suitable alternatives for the development of (68)Ga radiopharmaceuticals.
Abstract: Three phosphinic acid 1,4,7-triazacyclononane (TACN) derivatives bearing methylphosphinic (TRAP-H), methyl(phenyl)phosphinic (TRAP-Ph), or methyl(hydroxymethyl)phosphinic acid (TRAP-OH) pendant arms were investigated as members of a new family of efficient Ga3+ chelators, TRAP ligands (triazacyclononane phosphinic acids). Stepwise protonation constants of ligands and stability constants of their complexes with Ga3+, selected divalent metal, and Ln3+ ions were determined by potentiometry. For comparison, equilibrium data for the metal ion–NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) systems were redetermined. These ligands exhibit high thermodynamic selectivity for Ga3+ over the other metal ions (log KGaL – log KML = 7–9) and a selective complexation of smaller Mg2+ over Ca2+. Stabilities of the Ga3+ complexes are dependent on the basicity of the donor atoms: [Ga(NOTA)] (log KGaL = 29.6) > [Ga(TRAP-OH)] (log KGaL = 23.3) > [Ga(TRAP-H)] (log KGaL = 21.9). The [Ga(TRAP-OH)] complex exhibits unusual re...

99 citations

Journal ArticleDOI
TL;DR: The synthesis of novel water-soluble and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable neuropeptides and a chelator of the positron emitter (68)Ga as a PET reporter for in vivo tracking biodistribution is developed.
Abstract: New tools and techniques to improve brain visualization and assess drug permeability across the blood–brain barrier (BBB) are critically needed. Positron emission tomography (PET) is a highly sensitive, noninvasive technique that allows the evaluation of the BBB permeability under normal and disease-state conditions. In this work, we have developed the synthesis of novel water-soluble and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable neuropeptides and a chelator of the positron emitter 68Ga as a PET reporter for in vivo tracking biodistribution. The small GNPs (2 nm) are stabilized and solubilized by a glucose conjugate. A NOTA ligand is the chelating agent for the 68Ga, and two related opioid peptides are used as targeting ligands for improving BBB crossing. The radioactive labeling of the GNPs is completed in 30 min at 70 °C followed by purification via centrifugal filtration. As a proof of principle, a biodistribution study in rats is performed for the different 68Ga-GNP...

96 citations

Journal ArticleDOI
TL;DR: The key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands.
Abstract: The field of 18F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [18F]-radiotracers were generated by the direct attachment of 18F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an 18F-group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [18F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [18F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [18F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET.

80 citations

References
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Journal Article
TL;DR: The surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition, are explored and the rational approaches in the design as well as the biological performance of such constructs are assessed.
Abstract: The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

3,413 citations

Journal ArticleDOI
TL;DR: An overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd–based contrast agents.
Abstract: In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed.

531 citations

Journal ArticleDOI
TL;DR: Brief analysis of the micellization process and micelle properties shows that micelles made of amphiphilic co-polymers seem to be the most attractive for practical application.

459 citations

Journal ArticleDOI
TL;DR: Thermodynamic binding constants for gallium complexation at the two specific metal binding sites of human serum transferrin at pH 7.4 and 5 mM NaHCO3 have been determined by UV difference spectroscopy and are discussed in relation to the thermodynamics of transferrin binding of Fe3+.
Abstract: Gallium-67 is widely used as an imaging agent for tumors and inflammatory abscesses. It is well established that Ga3+ travels through the circulatory system bound to the serum iron transport protein transferrin and that this protein binding is an essential step in tumor localization. However, there have been conflicting reports on the magnitude of the gallium-transferrin binding constants. Therefore, thermodynamic binding constants for gallium complexation at the two specific metal binding sites of human serum transferrin at pH 7.4 and 5 mM NaHCO3 have been determined by UV difference spectroscopy. The conditional constants calculated for 27 mM NaHCO3 are log K1 = 20.3 and log K2 = 19.3. These results are discussed in relation to the thermodynamics of transferrin binding of Fe3+ and to previous reports on gallium binding. The strength of transferrin complexation is also compared to that of a series of low molecular weight ligands by using calculated pM values (pM = -log [Ga-(H2O)6]) to express the effective binding strength at pH 7.4.

300 citations

Journal ArticleDOI
TL;DR: The present work investigates the possibility of a rapid estimation of critical micelle concentration (cmc) of surfactants by means of soluble fluorescent probes and is independent of the cmc value within a wide range of concentrations.

213 citations