synthesis of MRI contrast agents Research Papers (original) (raw)

2025

Magnetic Resonance Imaging (MRI) is a diagnostic procedure used in the field of radiology to obtain high-resolution images of soft tissue. MRI uses the 1H NMR signal of water molecules located in the body. MRI takes advantage of the differences in the density of protons (water content) and the longitudinal (T1) and transverse (T2) relaxation times of the protons in tissue. By means of the administration of paramagnetic contrast agents, typically Gd3+ complexes, the image contrast is improved. The Morrow group has synthesized Fe3+ macrocyclic complexes as a promising new class of MRI contrast agents. HOPO ligands, a class of compounds that are heterocyclic and possess a hydroxyl group ortho to a ketone, are known iron chelators . Studies will be presented on derivatizing these HOPOs, and coupling them to the macrocyclic Fe(III) complex, to make labile iron pool -responsive contrast agents that can be used in MRI imaging. Studies to determine the selectivity of metal ion binding and the effect of the HOPO on the MRI relaxivity of the iron complexes will be discussed.

2025

Ce travail de thèse a été effectué au laboratoire de Reconnaissance Ionique et Chimie de Coordination du CEA Grenoble dirigé par Pascale Maldivi, que je remercie pour m'avoir accueilli au sein de son équipe. Je remercie Marinella Mazzanti qui a dirigé cette thèse, pour m'avoir suivi pendant ses trois ans, pour avoir toujours été disponible et pour m'avoir transmis son enthousiasme pour la chimie des lanthanides. Ce sujet a été pour moi l'occasion d'élargir mon horizon chimique grâce à l'opportunité qu'elle m'a offerte à travers ce sujet de thèse. Je voudrais remercier le professeur Jens Hasserodt et le docteur Loïc Charbonnière pour m'avoir fait l'honneur d'examiner ce mémoire en qualité de rapporteurs. Merci beaucoup pour le temps que vous avez pris pour lire et juger ce travail de thèse. Je remercie également le docteur Sarah Catoen et le professeur Fabrice Thomas pour l'intérêt qu'ils ont témoigné pour ce travail en acceptant de faire partie du jury de cette thèse. Je souhaite remercier tout particulièrement Pascal Fries, dont l'aide a été très précieuse au cours de ces trois ans, que ce soit pour les interprétations théoriques des résultats expérimentaux, pour les différentes expériences de relaxométrie ainsi que pour la relecture attentive du manuscrit. Je tiens à remercier Daniel Imbert pour les mesures de luminescence, ainsi que pour son aide pour la synthèse organique et les mesures de physico-chimie. Je tiens également à remercier Christelle Gâteau pour la synthèse des dérivés de la dpaa ainsi pour son aide et ses conseils pour la synthèse organique en général. En grand merci à Lydia Plassais qui m'a beaucoup aidé pour le développement des synthèses des ligands basés sur le 1,4,7 triazacyclononane. Je remercie Lother Helm pour m'avoir accueilli quelques jours au sein de son équipe à Lausanne et pour son aide pour les mesures de RMN de l' 17 O. Un grand merci également à Hugues Jacquard pour m'avoir aidé au laboratoire pendant ces dix jours.

2024

Depuis quelques annees, la recherche et le developpement dans le domaine des materiaux electroluminescents suscite de plus en plus d’interet. La crise energetique que nous connaissons actuellement motive un changement de mentalite de la societe, de plus en plus soucieuse d’economiser l’energie. Peu a peu, la commercialisation de diodes electroluminescentes telles que les LEDs (Light-Emitting Diodes) ou les OLEDs (Organic Light-Emitting Diodes) s’est implantee et elle connait aujourd’hui un essor considerable. Neanmoins, de nombreuses ameliorations doivent encore etre apportees afin d’en optimiser les proprietes. C’est dans cette thematique des materiaux electroluminescents que s’est focalise notre travail. La preparation de nouveaux composes et l’etude de leurs proprietes photophysiques representent en effet des etapes determinantes et indispensables a la fabrication de ces dispositifs. Notre travail s’est concentre plus particulierement sur des complexes de Rh(III), Ir(III) et Ru(I...

2024, International Journal of Applied Pharmaceutics

Objective: In this study, Ascorbic acid-coated Super-Paramagnetic Iron Oxide Nanoparticles (AA-SPIONs) were synthesized, optimized, and further evaluated. Methods: The nanoparticles were synthesized using the co-precipitation method, optimized by Box-Behnken Design (Design Expert® software). The formulation was then characterized for several in vitro attributes such as particle size distribution, zeta potential, Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Vibration Sample Magnetometry (VSM). Results: An optimized formulation was designed and synthesized. It showed an average size of ~260 nm with 24 mV zeta potential. The small size and electrostatic stability suggested an even distribution of particles in the bloodstream. FTIR revealed the interaction of AA with iron oxide. XRD studies and DSC thermograms ascertained the crystallinity of the iron formulation complying that the particles behaved as a single-domain magnetic crystal. The glass transition temperature of the coated nanoparticles was found to be 135.463ºC. Vibration sample magnetometry displayed the saturation magnetization value to be 2.87 emu g‾ 1 , which indicated the retained super-paramagnetic nature of the nanoparticles. Conclusion: The results were in concordance with the aim of this research work.

2024, HAL (Le Centre pour la Communication Scientifique Directe)

2024, Journal of Radiation Research and Applied Sciences

Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab in the form of 147 Gd-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer. 147 Gd radionuclide emits grays that can be used in SPECT modality, but because of technical constraint, 147 Gd radionuclide was simulated by its radioisotope, 153 Gd. Gd-DOTA complex has also been known as good MRI contrast agent. PAMAM G3.0 is useful to concentrate Gd-DOTA compelexes in large quantities, thus minimizing the number of trastuzumab molecules used. Trastuzumab is human monoclonal antibody that can spesifically interact with HER-2. Synthesis of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was initiated by conjugating DOTA NHS ester ligand with PAMAM G3.0 dendrimer. The DOTA-PAMAM G3.0 produced was conjugated to trastuzumab molecule and labeled with 153 Gd. Characterization DOTA-PAMAM G3.0-trastuzumab immunoconjugate was performed using HPLC system equipped with SEC. The formation of immunoconjugate was indicated by the shorter retention time (6.82 min) compared to that of trastuzumab (7.06 min). Radiochemical purity of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was >99% after purification process by PD-10 desalting column. Radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab compound was stable at room temperature and at 2e8 0C as indicated by its radiochemical purity 97.6 ± 0.5%e99.1 ± 0.5% after 144 h storage.

2024, TechConnect Briefs

Background: Magnetic Resonance Imaging (MRI) is a powerful non-invasive technique that provides highresolution anatomical images of biological tissue based on their inherent physio-chemical properties. The signal from MRI can be modulated by contrast agents, which can be specifically directed to cells and molecules of interest, thereby providing an opportunity for targeted imaging. Aims: We propose to extend previous work that has used very high-resolution MRI to characterize atherosclerotic plaque in mice. Through targeted imaging of cells and molecules involved in mouse atherosclerosis, pathological processes and their response to interventions can be imaged in vivo. Aim 1 was to develop and refine gadoliniumapoferritin nano-particles that have shown great potential as relaxivity agents for MR contrast studies. Aim 2 was image antibody-conjugated iron-oxide micro-beads (0.9 µm)). Aim 3 was applied using these imaging strategies using high field strength MRI (11.7 T/21 T) to interrogate processes of inflammation and thrombosis in vascular models. Targeting can be accomplished with established and novel antibodies developed by phage display (against active forms of fibrin and glycoprotein IIbIIIa). Methods: Molecular imaging probes were synthesized and characterized in vitro. Arterial injury was associated with a sequence of molecular and cellular events that result in intimal hyperplasia and, in the apolipoprotein E-deficient mouse, results in accelerated atherosclerosis. Results: This model exhibited molecular imaging targets whose spatial and temporal expression was established. These features, in conjunction with straight, superficial course of the femoral artery makes it an ideal imaging target to examine the pathology of atherothrombosis noninvasively in vivo and to measure the effects of interventions. Conclusion: The approach of molecular imaging by using antibody-conjugated superparamagnetic contrast agents may provide unique opportunity of microimaging in clinical set up.

2024

Right click to open a feedback form in a new tab to let us know how this document benefits you. This Comment is brought to you for free and open access by the Law Journals at UKnowledge.

2024, European Journal of Medicinal Chemistry

A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self-immolative moiety is presented. Synthesis of the ligand is convenient and relatively high yielded. Moreover, it enables synthesis of many derivatives, both in the amino-phenol and aminal fragment (various heterocycles). Once the final hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to hydrolysis. Bioactivation by b-galactosidase cleaves the glycosylic bond and a spontaneous collapse of the aminal fragment occurs, thus leading to a pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4-triazole and benzotriazole derivatives.

2024, Scientific Reports

A new bismuth-based CT agent was synthesized through a facile synthesis strategy. The in vitro stability, toxicity and CT performance were evaluated. The in vivo imaging performance was investigated using three different doses (0.5, 1.2 and 5 mmol/kg) and the result obtained at 1.2 mmol/kg was compared with the clinically approved CT agent iopamidol at the same dosage.

2024, ChemistrySelect

Funding from NSERC of Canada (Discovery Grant, CREATE, and USRA), the CFI (John R. Evans Leaders Fund), the CIHR, the Workers' Compensation Board of Alberta, and the University of Calgary's Eyes High Postdoctoral program is acknowledged. A. Vena and J. Collette's assistance in preparing cell cultures and analyzing cytotoxicity data, P. Lai and Prof. E.J. Prenner's assistance in preliminary toxicity studies, and J.-D. Jutras' assistance with MR measurements on the 3-T scanner are acknowledged.

2024, Proceedings of the National Academy of Sciences

Significance This work shows that iron oxide species as small as 1 nm in diameter can exhibit superparamagnetic properties and act as potent contrast agents for MRI. Because of their small size, the resulting particles effectively permeate dense biological tissue and undergo ultrasound-facilitated delivery from the vasculature to the brain. They also exhibit T 1 -weighted contrast-inducing properties similar to widely used paramagnetic MRI contrast agents but with far higher potency per molecule. Single-nanometer iron oxide agents, therefore, constitute a beneficial basis for the development of molecular imaging probes designed to detect targets in T 1 -weighted MRI. They might also function as alternatives to widely used gadolinium-based MRI agents in clinical contexts where gadolinium-related toxicity is a concern.

2024, HAL (Le Centre pour la Communication Scientifique Directe)

2024

The drug molecule vectorization is a very promising approach in terms of both medical and economical factors for the delivery of active substances with low bioavailability. In this context, the star polymers and dendrimers, symmetrical and branched macromolecules, seem to be more attractive solutions. Indeed, these structures can effectively combine a high stability in biological media and the ability to encapsulate active ingredients. Thanks to the well-defined architecture, they can achieve a high level of reproducibility of results, while avoiding the problem of polydispersity. In recent years, many dendritic structures have been proposed; however, the design of new effective dendritic nanocarriers is still relevant. This is due to many reasons such as related to biocompatibility, encapsulation efficiency of therapeutic agents, as well as economic reasons. In this project, new branched biocompatible macromolecules were designed, synthesized and evaluated. To increase their effectiveness as encapsulation agents for hydrophobic active principles, the structures of the proposed macromolecules include a hydrophobic central core on the basis of porphyrin, decanediol or modified triolein, and also a hydrophilic outer layer based on succinic acid and polyethylene glycol. The choice of structural elements of future dendrimers was based on the data on their biocompatibility and the results of our preliminary synthesis works, as well as the in silico simulations performed by using the method of molecular mechanics. The preliminary studies allowed for selecting the most promising compounds to effectively form polyesters macromolecules in well controlled manner, as well as to assess in advance the ability of future dendrimers to capture a drug molecule (itraconazole). During this phase, several new intermediates were obtained. The optimization of reaction conditions leading to high yields was performed. Based on the preliminary work, the assembly of new dendrimers of first and second generations was performed, by using the divergent and convergent synthesis approaches. The structures of new compounds were characterized by proton and 13 C carbon NMR, FTIR, UV-Vis, elemental analysis, mass spectrometry, and GPC techniques. The biocompatibility of products was evaluated by cytotoxicity tests with MTT on murine RAW 262.7 macrophages. The ability to encapsulate hydrophobic active principles was studied by testing with itraconazole, an antifungal agent with low bioavalability. The size of nanoparticles formed in aqueous solutions was measured by the DLS technique. These iv measurements showed that all dendritic structures tend to form micelles, which excludes their application as unimolecular nanocapsules. The antifungal activity of itraconazole formulations with dendrimers was studied in a kind of a pathogenic fungus Candida albicans. These tests lead to the conclusion that to ensure the effectiveness of treatment, more control over the release of the active ingredient has been needed.

2024, PLoS ONE

The current study was carried out to test the potential of a new nanomaterial (Spago Pix) as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r 1) of approximately 30 (mM Mn) 21 s 21 (60 MHz). The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II) ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7) showed a contrast enhancement factor of 1.8 (tumor versus muscle) at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI.

2024, Sci

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

2024, Sci

Pregnancy is a delicate state, during which timely investigation of possible physiological anomalies is essential to reduce the risk of maternal and fetal complications. Medical imaging encompasses different technologies to image the human body for the diagnosis, course of treatment management, and follow-up of diseases. Ultrasound (US) is currently the imaging system of choice for pregnant patients. However, sonographic evaluations can be non-effective or give ambiguous results. Therefore, magnetic resonance imaging (MRI), due to its excellent tissue penetration, the possibility of acquisition of three-dimensional anatomical information, and its high spatial resolution, is considered a valid diagnostical alternative. Nevertheless, currently employed contrast agents to improve the MRI image quality are harmful to the fetus. Because of their ability to cross the placenta, their use on pregnant patients is avoided. This review will firstly recapitulate the most common non-obstetrical,...

2023, Nanoscale Research Letters

Novel magnetic composite nanoparticles (MCPs) were successfully synthesized by ex situ conjugation of synthesized ZnO nanoparticles (ZnO NPs) and Fe 3 O 4 NPs using trisodium citrate as linker with an aim to retain key properties of both NPs viz. inherent selectivity towards cancerous cell and superparamagnetic nature, respectively, on a single system. Successful characterization of synthesized nanoparticles was done by XRD, TEM, FTIR, and VSM analyses. VSM analysis showed similar magnetic profile of thus obtained MCPs as that of naked Fe 3 O 4 NPs with reduction in saturation magnetization to 16.63 emu/g. Also, cell viability inferred from MTT assay showed that MCPs have no significant toxicity towards noncancerous NIH 3T3 cells but impart significant toxicity at similar concentration to breast cancer cell MDA-MB-231. The EC50 value of MCPs on MDA-MB-231 is less than that of naked ZnO NPs on MDA-MB-231, but its toxicity on NIH 3T3 was significantly reduced compared to ZnO NPs. Our hypothesis for this prominent difference in cytotoxicity imparted by MCPs is the synergy of selective cytotoxicity of ZnO nanoparticles via reactive oxygen species (ROS) and exhausting scavenging activity of cancerous cells, which further enhance the cytotoxicity of Fe 3 O 4 NPs on cancer cells. This dramatic difference in cytotoxicity shown by the conjugation of magnetic Fe 3 O 4 NPs with ZnO NPs should be further studied that might hold great promise for the development of selective and site-specific nanoparticles.

2023, PLOS ONE

2023

Novel biocompatible poly(ethylene glycol) (PEG)-stabilized CoO nanoparticles have been synthesized. The particles exhibited a near-infrared laser-based photoacoustic signal that was 11 times stronger than that of our previously developed gadolinium oxide nanoparticles. The value of r 2 /r 1 determined by 7 T MRI at room temperature was similar to that of a clinically-used negative MRI contrast agent, Resovist ®. These results indicate that the present PEG-stabilized CoO nanoparticles may be highly effective as a bimodal contrast agent for photoacoustic and magnetic resonance imaging.

2023, Canadian Young Scientist Journal

Grâce à un dépistage de deux séries d'agents de contrastes, DOTA (acide 1,4,7,10-tétraazacyclododécane-1,4,7,10-tétraacétique) et DTPA (acide diéthylènetriaminepentaacétique), ce projet vise à trouver la meilleure méthode afin de mesurer la thrombine dans le sérum. L'utilisation de cette technologie avec I am grateful to Carleton University for providing the DNA synthesizer, the Gel electrophoresis setup, the UV-Vis spectrometer, and access to the 1.5 T MRI (Ottawa Hospital) through a collaboration with Dr. Eve Tsai. I am also deeply grateful to Erin McConnell and Dr. Maria DeRosa for their guidance and supervision.

2023, Journal of Radiation Research and Applied Sciences

2023

La synthese colloidale et la fonctionnalisation de nanoparticules luminescentes sont indispensables a la fois pour l'utilisation comme particules individuelles dans des sondes biologiques et pour l'elaboration de materiaux transparents et luminescents pour l'optique integree. La synthese de reseaux organises de nanoparticules par croissance confinee dans des films mesoporeux pourrait permettre d'exploiter les effets optiques collectifs.

2023, Molecular Crystals and Liquid Crystals

2023, Dalton Transactions

General procedures. NMR spectra were recorded on an Advance DMX 200 Brucker spectrometer. Chemical shifts are reported in ppm with solvent as internal reference. ESMS were recorded on a Thermo Scientific (LXQ) spectrometer. Electronic absorption spectra were recorded on a Varian CARY 50 probe UV/vis spectrometer. Materials. Solvents and starting materials were obtained from Aldrich, Fluka, Acros, and Alfa. They were used without further purification unless otherwise stated. Methyl (S)-2amino-4-(tert-butoxycarbonylamino)butanoate hydrochloride (b) was purchased from BACHEM (Weil am Rhein, Germany).Water and H 2 O refer to high purity water with resistivity value of 18 MΩ•cm, obtained from the "Millipore/MilliQ" purification system. Lanthanide chloride salts were purchased from Aldrich. The precise metal ion content was determined by colorimetric titration in acetate buffer (pH = 4.5) using a standardized H 2 Na 2 edta solution (Merck) and Xylenol orange as indicator. 6-Chloromethylpyridine-2carboxylic acid ethyl ester (a) was prepared according to literature procedure. 1 Relaxivity measurements. The Gd.1 was prepared in situ by mixing the appropriate amounts of ligand and GdCl 3 .6H 2 O (99.99%; Aldrich) in H 2 O followed by adjustment of the pH with NaOH aqueous solution (pH = 7.4). Gd.2 Gd.3 and Gd.4 where taken up in H 2 O followed by adjustment of the pH with NaOH aqueous solution (pH = 7.4). The pH of the Gd2.QD, Gd.3.QD and Gd.4.QD suspension were prepared as above, for relaxivity measurements at 7.4. The resulting solutions/suspensions were placed in a 1.7 mm diameter capillary which was sealed. The absence of free gadolinium was checked in all samples by the xylenol orange

2023, Journal of Magnetism and Magnetic Materials

Iron oxide nanospheres and nanocubes modified with carboxyphenyl porphyrin and their magnetic, optical properties and photocatalytic activities in room temperature amide synthesis,

2023, Magnetic resonance in medicine

Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)-AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin-fibronectin (FB-FN) complex. The peptide CREKA (Cys-Arg-Glu-Lys-Ala), targeting the FB-FN complex in the reactive stroma of the tumor, was synthesized by solid phase peptide synthesis (SPPS) and conjugated to the tetramer dL-(Gd-AAZTA) . The resulting probe was characterized by H relaxometry, tested in vitro on FB clots and in vivo on an orthotopic mouse model of PCa. CREKA-dL-(Gd-AAZTA) showed a remarkable relaxivity of 18.2 m (0.47 T, 25°C) because of the presence of 2 water molecules (q = 2) in the inner coordination sphere of each Gd ion, whose rotational motion (τ ) is lengthened as the result of the relatively high molecular weight. The probe displayed a detectable ...

2023, Inorganic Chemistry

Four new Gd(III) complexes based on the 1,2-hydroxypyridinone chelator have been synthesized and evaluated as potential MRI contrast agents. Previously reported work examining Gd-TREN-1,2-HOPO (3) suggests that the 1,2-HOPO unit binds strongly and selectively to Gd(III), encouraging further study of the stability and relaxivity properties of this class of compounds. Among the new complexes presented in this paper are the homopodal Gd-Ser-TREN-1,2-HOPO (Gd-5) and three heteropodal bis-1,2-HOPO-TAM complexes (Gd-6, Gd-7, and Gd-8). Conditional stability constants were determined and all pGd values are in the range of 18.5 − 19.7, comparable to other analogous HOPO complexes and currently used commercial contrast agents. Relaxivities for all complexes are about twice those of commercial agents, ranging from 7.8 − 10.5 mM −1 s −1 (20 MHz; 25 °C), and suggest two inner-sphere water molecules in fast exchange. Luminescent measurements were used to verify the number of coordinated waters for Gd-5, and VT 17 O NMR experiments were employed for the highly soluble Gd-TREN-bis-1,2-HOPO-TAM-N3 (Gd-8) complex to measure a fast water exchange rate, 298 k ex = 1/τ M , of 5.1(±0.4) × 10 8 s −1 (298 τ M ∼ 2 ns).

2023, Inorganic Chemistry

The variation of the size of the capping scaffold which connects the hydroxypyridonate (HOPO) binding units in a series of tripodal chelators for gadolinium (Gd) complexes has been investigated. A new analogue of TREN-1-Me-3,2-HOPO (1) (TREN) tri(ethylamine)amine) was synthesized: TREN-Gly-1-Me-3,2-HOPO (2) features a glycine spacer between the TREN cap and HOPO binding unit. TRPN-1-Me-3,2-HOPO (3) has a propylene-bridged cap, as compared to the ethylene bridges within the TREN cap of the parent complex. Thermodynamic equilibrium constants for the acid−base properties of 2 and the Gd 3+ complexation strength of 2 and 3 were measured and are compared with that of the parent ligand. The most basic ligand is 2 while 3 is the most acidic. Both 2 and 3 form Gd 3+ complexes of similar stability (pGd) 16.7 and 15.6, respectively) and are less stable than the parent complex Gd-1 (pGd) 19.2). Two of the three complexes are more stable than the bis(methylamide)diethylenetriamine pentaacetate complex Gd(DTPA-BMA) (pGd) 15.7) while the other is of comparable stability. Enlargement of the ligand scaffold decreases the stability of the Gd 3+ complexes and indicates that the TREN scaffold is superior to the TRPN and TREN-Gly scaffolds. The proton relaxivity of Gd-2 is 6.6 mM-1 s-1 (20 MHz, 25°C, pH 7.3), somewhat lower than the parent Gd-1 but higher than that of the MRI contrast agents in clinical practice. The pH-independent relaxivity of Gd-2 is uncharacteristic of this family of complexes and is discussed.

2023, Contrast Media & Molecular Imaging

A series of new Gd(III) hydroxypyridonate complexes featuring a mesitylene (ME)-derived ligand cap has been prepared. Relaxometric characterization reveals that the complexes tend to form large aggregates in solution with slow tumbling rates, as estimated from NMRD analysis, and unique pH-dependent relaxivities. The solution behavior and relaxometric properties are compared to those observed for analogous TREN-capped compounds, and the potential for use of these new ME-capped complexes as pH-responsive MRI contrast agents is explored.

2023, Journal de Physique

2014 Nous présentons une étude du spectre de résonance magnétique des protons appartenant aux ions NH+4 dans l'alumine 03B2 à l'ammonium, à basse température. Nous montrons que les ions en site Beevers-Ross sont soumis à une rotation-tunnel rapide qui se manifeste par un rétrécissement de la raie de résonance, alors que les ions en site mid-oxygen apparaissent comme statiques et donnent une raie large. En opérant sur un échantillon mixte sodium-ammonium, nous avons pu isoler le spectre des ions Beevers-Ross. L'application de la théorie du spectre des protons de l'ion ammonium dans le cas d'un rétrécissement par la rotation-tunnel, formalisée par Lalowicz et al., fournit une description remarquablement bonne des spectres expérimentaux et permet de déterminer l'orientation d'équilibre du tétraèdre NH4 dans le site Beevers-Ross. Abstract. 2014 We present a study of the NMR spectrum of protons belonging to ammonium ions in ammonium 03B2alumina, at low temperature. We show that ammonium ions in Beevers-Ross sites undergo a fast rotational tunnelling which gives rise to a strong narrowing of their NMR spectrum, while ammonium ions in mid-oxygen sites are static and give a broad spectrum. By examining a mixed sodium-ammonium sample, we have been able to separate the spectrum of Beevers-Ross ions. The theory of magnetic resonance of protons belonging to NH+4 ions submitted to a fast rotational tunnelling, as formalized by Lalowicz et al., is applied. It yields a very nice agreement with the experimental spectrum. This also allows the stable orientation of the NH4 tetrahedron in the Beevers-Ross site to be determined.

2023, Journal of Hazardous Materials

-Fe 2 O3 -Fe 2 O3-NH4OH@SiO2(APTMS) NPs with a large grafting density of amines H2N O O O Si Highlights  simple synthesis procedure of stabilized functionalized magnetic core@shell NPs  characterization of gradually synthesized magnetic NPs  clearly exposed role of each material in NPs  adsorption of Dy 3+ from aqueous solution of low concentration Dy 3+ at neutral pH ABSTRACT This paper deals with synthesis and characterization of novel -Fe2O3-NH4OH@SiO2(APTMS) nanoparticles formed from magnetic -Fe2O3 core, stabilized electrostatically in basic media NH4OH, doped with SiO2 shell and functionalized with 3-aminopropyltrimethoxysilane. The gradually synthesized nanoparticles are characterized in order to analyze their structural, morphology, thermogravimetry, surface area and charge, and magnetic properties. The novel synthesized -Fe2O3-NH4OH@SiO2(APTMS) nanoparticles are suitable to adsorb dysprosium ions (Dy 3+), as one of the most critical rare earth elements, from aqueous solution. The Dy 3+ adsorption from aqueous solution follows a pseudo-second order kinetic model and the adsorption equilibrium data fits well to the Temkin isotherm. Thermodynamic studies imply that the adsorption process is endothermic and spontaneous in nature. The maximum adsorption efficiency for Dy 3+ from aqueous solution with 2•10-6 M concentration of Dy 3+ is over 90% at pH 7.

2023

La rupture de la plaque atheromateuse est la cause d'environ 70% des attaques cardiaques soudaines et souvent mortelles. Les lesions atherosclereuses sont des epaississements focaux riches en lipides dans les parois des arteres. Developper un (ou des) agent de contraste ciblant est d'un interet clinique crucial pour evaluer les composants a l’origine du risque de rupture. L'imagerie moleculaire necessite des sondes hautement sensibles et specifiques constituees de ligands pour le ciblage. Les ligands sont ici des fragments d’anticorps humains recombinants (scFv) qui sont fonctionnalises sur des nanoparticules multimodales chargees (1) d'oxyde de fer pour l'imagerie par resonance magnetique (IRM) non-invasive et (2) de fluorophores dans le proche infrarouge (PIR) pour l'imagerie de fluorescence au niveau tissulaire et cellulaire. Les particules a base d’oxyde de fer (USPIOs) sont employees en IRM pour leurs proprietes superparamagnetiques qui induisent localem...

2023, ChemistrySelect

Benzothiazole derivatives are highly selective and an antitumor therapeutic in vitro and in vivo, highlighting the compound 2-(4'-aminophenyl) benzothiazole (ABT), which exhibits nanomolar concentration activity in vitro against some human breast cancer cells in humans. In this work, we designed new contrast agents based on the structural modification of ABT by complexing them with manganese in order to obtain para-magnetic complexes for efficient diagnosis of breast cancer. The new agents were evaluated by docking studies that allowed investigating interactions and the mode of connection between the active site of the enzyme and the compounds studied. The theoretical and experimental results both indicate that Compound 57 is a promising contrast agent.

2023, Inorganic Chemistry

To evaluate the effect of ligand geometry on the coordination number, number of inner-sphere water molecules, and affinity for anions of the corresponding lanthanide complex, six tris-bidentate 1,2-hydroxypyridonate (HOPO) europium(III) complexes with different cap sizes were synthesized and characterized. Wider or more flexible ligand caps, such as in Eu III-TREN-Gly-HOPO and Eu III-3,3-Gly-HOPO, enable the formation of nine-coordinate europium(III) complexes bearing three inner-sphere water molecules. In contrast, smaller or more rigid caps, such as in Eu III-TREN-HOPO, Eu III-2,2-Li-HOPO, Eu III-3,3-Li-HOPO, and Eu III-2,2-Gly-HOPO, favor eight-coordinate europium(III) complexes that have only two inner-sphere water molecules. Notably, there is no correlation between the number of inner-sphere water molecules and the affinity of the Eu(III) complexes for phosphate. Some q = 2 (Eu III-TREN-HOPO, Eu III-3,3-Li-HOPO, and Eu III-2,2-Gly-HOPO) and some q = 3 (Eu III-TREN-Gly-HOPO) complexes have no affinity for anions, whereas one q = 2 complex (Eu III-2,2-Li-HOPO) and one q = 3 complex (Eu III-3,3-Gly-HOPO) have a high affinity for phosphate. For the latter two systems, each inner-sphere water molecule is replaced with a phosphate anion, resulting in the formation of EuLPi 2 and EuLPi 3 adducts, respectively.

2023, Inorganic Chemistry

Although recognition of hard anions by hard metal ions is primarily achieved via direct coordination, electrostatic and hydrogen-bonding interactions also play essential roles in tuning the affinity of such supramolecular receptors for their target. In the case of Eu III hydroxypyridinone-based complexes, the addition of a single charged group (−NH 3 + , −CO 2 − , or −SO 3 −) or neutral hydrogen-bonding moiety (−OH) peripheral to the open coordination site substantially affects the affinity of the metal receptor for phosphate in water at neutral pH. A single primary ammonium increases the first association constant for phosphate in neutral water by 2 orders of magnitude over its neutral analogue. The addition of a peripheral alcohol group also increases the affinity of the receptor but to a lesser degree (21-fold). On the other hand, negatively charged complexes bearing either a carboxylate or sulfate moiety have negligible affinity for phosphate. Interestingly, the peripheral group also influences the stoichiometry of the lanthanide receptor for phosphate. While the complex bearing a −NH 3 + group binds phosphate in a 1:2 ratio, those with −OH and H (control) both form 1:3 complexes. Although the positively charged Eu III-Lys-HOPO has the highest K a1 for phosphate, a greater increase in luminescence intensity (36-fold) is observed with the neutral Eu III-Ser-HOPO complex. Notably, whereas the affinity of the Eu III complexes for phosphate is substantially influenced by the presence of a single charged group or hydrogen-bond donor, their selectivity for phosphate over competing anions remains unaffected by the addition of the peripheral groups.

2023

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

2023

La voie orale est le mode d’administration le plus utilise pour les medicaments. Ce mode d’administration presente de nombreux avantages tels que la facilite d’administration et une grande observance par les patients. Une des principales limitations de l’utilisation de la voie orale pour l’administration de molecules actives est que ces molecules doivent traverser les membranes biologiques pour rejoindre la circulation sanguine systemique et atteindre leur site d’action. C’est cette etape de passage transmembranaire qui determine la biodisponibilite de la molecule active (ou principe actif, PA). De nombreuses molecules presentent une activite therapeutique interessante mais leur developpement galenique n’est pas envisageable du fait de leur biodisponibilite trop faible. Dans cette these, le principe de la retention magnetique a ete etudie. Nous avons cherche a prouver que le fait de retenir, a l’aide d’un aimant, une formulation magnetique contenant un principe actif, peu permeable,...

2023, Journal of Radiation Research and Applied Sciences

2023, JBIC Journal of Biological Inorganic Chemistry

How to cite TSpace items Always cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page. This article was made openly accessible by U of T Faculty. Please tell us how this access benefits you. Your story matters.

2023, Chemical Science

MnAMP, a cell-trappable pro-contrast agent gets enzymatically activated and accumulated intracellularly to provide a strong MRI signal for cell labeling.

2023, Scientific reports

Despite preliminary confidence on biosafety of polymer coated iron oxide nanoparticles (SPIONs), toxicity concerns have hampered their clinical translation. SPIONs toxicity is known to be due to catalytic activity of their surface and release of toxic Fe ions originating from the core biodegradation, leading to the generation of reactive oxygen species (ROS). Here, we hypothesized that a double-layer polymeric corona comprising of dextran as an interior, and polyethylene glycol (PEG) as an exterior layer better shields the core SPIONs. We found that ROS generation was cell specific and depended on SPIONs concentration, although it was reduced by sufficient PEG immobilization or 100 µM deferoxamine. 24 h following injection, PEGylated samples showed reduction of biodistribution in liver, heterogenous biodistribution profile in spleen, and no influence on NPs blood retention. Sufficient surface masking or administration of deferoxamine could be beneficial strategies in designing and c...

2023, European Journal of Inorganic Chemistry

The tumor targeting is essential in order to use excellent theranostic properties of gadolinium oxide (Gd2O3) nanoparticles (GNPs) as high-performance positive magnetic resonance imaging (T1 MRI) contrast agents, X-ray computed tomography (CT) contrast agents, and gadolinium neutron capture therapy (GdNCT) agents. Among these applications, the tumor targeting T1 MRI was investigated in this study. To this end, we employed cyclic RGDs (cRGDs) as tumor targeting ligands to coat the ultrasmall GNPs (particle diameter = 1.0-2.5 nm). Five types of commercial cRGDs were used in the coating. The cRGD-coated GNPs (cRGD-GNPs) were prepared through one-pot synthesis. They exhibited longitudinal water proton relaxivities (r1s) of 10.0-18.7 s-1 mM-1 with r2/r1 ratio of 1.4-1.7 (r2 = transverse water proton relaxivity), which were 3-5 times higher than those of commercial Gd-chelates. The in vivo tumor targeting of the cRGD-GNPs was demonstrated by taking T1 MR images in a model mouse with liver tumor using one of five cRGD-GNP sample solutions prepared. Approximately three times greater contrast enhancements in T1 MR images in the tumor region of the liver were observed compared to the normal part of the liver after intravenous administration. These results demonstrated that cRGD-GNPs should be the potential tumor-targeting T1 MRI contrast agent. Results and Discussion Particle diameter (d) and crystal structure of cRGD-GNPs

2023, Journal of Composites Science

A contrast agent with specific characteristics is essential for high-quality magnetic resonance imaging (MRI). It plays a crucial role in enhancing the visibility of certain tissues and structures, making it imperative for diagnostic procedures. Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as a promising alternative to traditional contrast agents for MRI due to their non-toxicity and superior magnetic properties. However, a suitable surface coating strategy is needed to produce polymer-coated SPIONs with controllable sizes in order to enhance their stability and biocompatibility. This study presents a novel one-pot synthesis method for the production of highly stable polyvinylpyrrolidone (PVP)-coated SPIONs. By systematically manipulating the physicochemical properties of SPIONs, the effect of different molecular weights of PVP was studied. The results showed that SPIONs coated with PVP with molecular wight 40,000 g/mol (40 K) exhibited a high magnetization (Ms =...

2023

A majority of MRI procedures requiring intravascular injections of contrast agents are performed with paramagnetic chelates. Such products induce vascular signal enhancement and they are rapidly excreted by the kidneys. Unfortunately, each chelate is made of only one paramagnetic ion, which, taken individually, has a limited impact on the MRI signal. In fact, the detection of molecular events in the nanomolar range using T1weighted MRI sequences requires the design of ultra-small particles containing hundreds of paramagnetic ions per contrast agent unit. Ultra-small nanoparticles of manganese oxide (MnO, 6–8 nm diameter) have been developed and proposed as an efficient and at least 1000 more sensitive “positive” MRI contrast agent. However no evidence has been found until now that an adequate surface treatment of these particles could maintain their strong blood signal enhancement, while allowing their rapid and efficient excretion by the kidneys or by the hepatobiliairy pathway. In...

2023, Journal of Radiation Research and Applied Sciences

2023, Comptes Rendus de l'Académie des Sciences - Series IV - Physics

Nous discutons les conditions d'observation et de caractérisation du transfert d'aimantation entre du xénon 129 polarisé par laser et des protons d'une protéine. Un tel phénomène est illustré sur la protéine de transfert non spécifique de lipides du blé.  2001 Académie des sciences/Éditions scientifiques et médicales Elsevier SAS xénon polarisé par laser / protéine / SPINOE / relaxation croisée First direct observation of magnetization transfer between laser-polarized xenon and protein protons

2023, Oriental Journal of Chemistry

In this work, we report synthesis and characterization of soy lecithin (SL) coated iron oxide nanoparticles by one step co precipitation method in an aqueous solution using ferrous and ferric salts (1:2), different values of SLP (0.0, 1.5 and 6 gr) and ammonia to adjust pH=10. Characterization of the samples (labeled as SPION, "SPION 1.5 and SPION 6) carried out using X-ray powder diffraction (XRD) patterns indicated formation of magnetite (Fe 3 O 4) nanoparticles with a calculated average crystalline size of 25 nm for naked Fe 3 O 4 , 13 nm for "SPION 1.5 " and 9 nm for "SPION 6 " nanoparticles by Sherrer's equation. FT-IR spectroscopy and Thermo-gravimetric analysis (TGA) were used to investigate the presence of "SL" on the nanoparticles surface. The images and morphology of the samples were examined on scanning electron microscope (SEM). Detailed chemical analysis of the nanoparticles was obtained from energy dispersive X-ray (EDX) data. To measure magnetic properties of the prepared samples, a Vibrating Sample Magnetometer (VSM) was used and a Dynamic Light Scattering (DLS) instrument was finally used to measure hydrodynamic diameter of the nanoparticles. The results revealed that the soybean lecithin was coated on Fe 3 O 4 nanoparticles surface and smaller particle size was obtained with increased concentrations of soybean lecithin.