Most cited article - PubMed ID 30167995
A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging
Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1H/19F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications.
- Keywords
- 19F magnetic resonance imaging, 19F magnetic resonance spectroscopy, Cell labeling, Fluorinated micelles,
- MeSH
- Staining and Labeling methods MeSH
- Phantoms, Imaging MeSH
- Fluorine chemistry MeSH
- Halogenation MeSH
- Cations * chemistry MeSH
- Contrast Media chemistry MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Micelles * MeSH
- Mice MeSH
- Cell Survival * drug effects MeSH
- Fluorine-19 Magnetic Resonance Imaging methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fluorine MeSH
- Cations * MeSH
- Contrast Media MeSH
- Micelles * MeSH
Diagnostics is an important part of medical practice. The information required for diagnosis is typically collected by performing diagnostic tests, some of which include imaging. Magnetic resonance imaging (MRI) is one of the most widely used and effective imaging techniques. To improve the sensitivity and specificity of MRI, contrast agents are used. In this review, the usage of metal-organic frameworks (MOFs) and composite materials based on them as contrast agents for MRI is discussed. MOFs are crystalline porous coordination polymers. Due to their huge design variety and high density of metal ions, they have been studied as a highly promising class of materials for developing MRI contrast agents. This review highlights the most important studies and focuses on the progress of the field over the last five years. The materials are classified based on their design and structural properties into three groups: MRI-active MOFs, composite materials based on MOFs, and MRI-active compounds loaded in MOFs. Moreover, an overview of MOF-based materials for heteronuclear MRI including 129Xe and 19F MRI is given.
- Keywords
- magnetic resonance imaging, metal−organic frameworks, multimodal imaging, nanomedicine, theranostics,
- MeSH
- Ions MeSH
- Contrast Media chemistry MeSH
- Metals chemistry MeSH
- Magnetic Resonance Imaging MeSH
- Metal-Organic Frameworks * chemistry MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Ions MeSH
- Contrast Media MeSH
- Metals MeSH
- Metal-Organic Frameworks * MeSH
Upconverting nanoparticles are attracting extensive interest as a multimodal imaging tool. In this work, we report on the synthesis and characterization of gadolinium-enriched upconverting nanoparticles for bimodal magnetic resonance and optical luminescence imaging. NaYF4:Gd3+,Yb3+,Tm3+ core upconverting nanoparticles were obtained by a thermal coprecipitation of lanthanide oleate precursors in the presence of oleic acid as a stabilizer. With the aim of improving the upconversion emission and increasing the amount of Gd3+ ions on the nanoparticle surface, a 2.5 nm NaGdF4 shell was grown by the epitaxial layer-by-layer strategy, resulting in the 26 nm core-shell nanoparticles. Both core and core-shell nanoparticles were coated with poly(ethylene glycol) (PEG)-neridronate (PEG-Ner) to have stable and well-dispersed upconverting nanoparticles in a biological medium. FTIR spectroscopy and thermogravimetric analysis indicated the presence of ∼20 wt % of PEG-Ner on the nanoparticle surface. The addition of inert NaGdF4 shell resulted in a total 26-fold enhancement of the emission under 980 nm excitation and also affected the T 1 and T 2 relaxation times. Both r 1 and r 2 relaxivities of PEG-Ner-modified nanoparticles were much higher compared to those of non-PEGylated particles, thus manifesting their potential as a diagnostic tool for magnetic resonance imaging. Together with the enhanced luminescence efficiency, upconverting nanoparticles might represent an efficient probe for bimodal in vitro and in vivo imaging of cells in regenerative medicine, drug delivery, and/or photodynamic therapy.
- Publication type
- Journal Article MeSH
As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.
- MeSH
- Glycogen administration & dosage MeSH
- Rats MeSH
- Drug Delivery Systems * MeSH
- Cell Line, Tumor MeSH
- Neoplasms drug therapy MeSH
- Antineoplastic Agents administration & dosage MeSH
- Theranostic Nanomedicine * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glycogen MeSH
- Antineoplastic Agents MeSH
Over the last few years, the development and relevance of 19F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.
- Keywords
- 19F MRI probe, Fluorine, Magnetic resonance imaging (MRI), Molecular imaging, Polymer,
- MeSH
- Fluorine chemistry MeSH
- Fluorocarbons chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Contrast Media chemistry MeSH
- Humans MeSH
- Molecular Probes chemistry MeSH
- Molecular Imaging instrumentation methods MeSH
- Mice MeSH
- Polymers chemistry MeSH
- Scattering, Radiation MeSH
- Reactive Oxygen Species metabolism MeSH
- Light MeSH
- Temperature MeSH
- Fluorine-19 Magnetic Resonance Imaging methods trends MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Fluorine MeSH
- Fluorocarbons MeSH
- Contrast Media MeSH
- Molecular Probes MeSH
- Polymers MeSH
- Reactive Oxygen Species MeSH
OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.
- Keywords
- Fluorine-19 magnetic resonance imaging, Lanthanide series elements, Macrocyclic ligand complexes, Molecular probes, Phosphinic acid complexes, Relaxation times,
- MeSH
- Chelating Agents chemistry MeSH
- Fluorine chemistry MeSH
- Ions MeSH
- Contrast Media chemistry MeSH
- Rats MeSH
- Lanthanoid Series Elements chemistry MeSH
- Ligands MeSH
- Magnetics MeSH
- Molecular Weight MeSH
- Oxazoles chemistry MeSH
- Pyrimidinones chemistry MeSH
- Fluorine-19 Magnetic Resonance Imaging * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one MeSH Browser
- Chelating Agents MeSH
- Fluorine MeSH
- Ions MeSH
- Contrast Media MeSH
- Lanthanoid Series Elements MeSH
- Ligands MeSH
- Oxazoles MeSH
- Pyrimidinones MeSH