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.
- Klíčová slova
- 19F magnetic resonance imaging, 19F magnetic resonance spectroscopy, Cell labeling, Fluorinated micelles,
- MeSH
- barvení a značení metody MeSH
- fantomy radiodiagnostické MeSH
- fluor chemie MeSH
- halogenace MeSH
- kationty * chemie MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely * MeSH
- myši MeSH
- viabilita buněk * účinky léků MeSH
- zobrazování fluorovou magnetickou rezonancí metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fluor MeSH
- kationty * MeSH
- kontrastní látky MeSH
- micely * MeSH
Fluorine magnetic resonance imaging (19F MRI) is a rapidly evolving research area with a high potential to advance the field of clinical diagnostics. In this review, we provide an overview of the recent progress in the field of fluorinated stimuli-responsive polymers applied as 19F MRI tracers. These polymers respond to internal or external stimuli (e.g., temperature, pH, oxidative stress, and specific molecules) by altering their physicochemical properties, such as self-assembly, drug release, and polymer degradation. Incorporating noninvasive 19F labels enables us to track the biodistribution of such polymers. Furthermore, by triggering polymer transformation, we can induce changes in 19F MRI signals, including attenuation, amplification, and chemical shift changes, to monitor alterations in the environment of the tracer. Ultimately, this review highlights the emerging potential of stimuli-responsive fluoropolymer 19F MRI tracers in the current context of polymer diagnostics research.
- MeSH
- chytré polymery chemie MeSH
- fluor chemie MeSH
- koncentrace vodíkových iontů MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- polymery chemie MeSH
- zobrazování fluorovou magnetickou rezonancí * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chytré polymery MeSH
- fluor MeSH
- kontrastní látky MeSH
- polymery MeSH
Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring-the dichloro[(±)-trans-N,N'-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region.
- Klíčová slova
- BSA binding, DNA binding, anticancer activity, antimicrobial activity, copper, cytotoxicity, metal complexes, urease inhibition,
- MeSH
- antitumorózní látky * farmakologie chemie MeSH
- buňky Hep G2 MeSH
- DNA metabolismus chemie MeSH
- fluor chemie MeSH
- komplexní sloučeniny * farmakologie chemie chemická syntéza MeSH
- lidé MeSH
- ligandy MeSH
- měď * chemie MeSH
- Schiffovy báze * chemie farmakologie MeSH
- sérový albumin hovězí chemie MeSH
- ureasa antagonisté a inhibitory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky * MeSH
- calf thymus DNA MeSH Prohlížeč
- DNA MeSH
- fluor MeSH
- komplexní sloučeniny * MeSH
- ligandy MeSH
- měď * MeSH
- Schiffovy báze * MeSH
- sérový albumin hovězí MeSH
- ureasa MeSH
In this study, we investigated the potential of long-range fluorine-carbon J-coupling for determining the structures of deoxyfluorinated disaccharides. Three disaccharides, previously synthesized as potential galectin inhibitors, exhibited through-space fluorine-carbon J-couplings. In our independent conformational analysis of these disaccharide derivatives, we employed a combination of density functional theory (DFT) calculations and nuclear magnetic resonance (NMR) experiments. By comparing the calculated nuclear shieldings with the experimental carbon chemical shifts, we were able to identify the most probable conformers for each compound. A model comprising fluoromethane and methane molecules was used to study the relationship between molecular arrangements and intermolecular through-space J-coupling. Our study demonstrates the important effect of internuclear distance and molecular orientation on the magnitude of fluorine-carbon coupling. The experimental values for the fluorine-carbon through-space couplings (TSCs) of the disaccharides corresponded with values calculated for the most probable conformers identified by the conformational analysis. These results unlock the broader application of fluorine-carbon TSCs as powerful tools for conformational analysis of flexible molecules, offering valuable insights for future structural investigations.
- Klíčová slova
- Conformation, DFT calculations, Fluorine, NMR spectroscopy, Saccharides,
- MeSH
- disacharidy * chemie MeSH
- fluor * chemie MeSH
- konformace sacharidů MeSH
- magnetická rezonanční spektroskopie * MeSH
- molekulární konformace MeSH
- teorie funkcionálu hustoty * MeSH
- uhlík chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance (19F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19F MR relaxation times. This study aims to explore the potential of micellar 19F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools.
- Klíčová slova
- clofazimine, fluorine‐19, magnetic resonance, nanoparticles, polymerization‐induced self‐assembly, theranostics,
- MeSH
- biokompatibilní materiály chemie MeSH
- fluor chemie MeSH
- fluorokarbony chemie MeSH
- halogenace MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely MeSH
- myši MeSH
- nanočástice * chemie terapeutické užití MeSH
- teranostická nanomedicína * MeSH
- zobrazování fluorovou magnetickou rezonancí * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- fluor MeSH
- fluorokarbony MeSH
- micely MeSH
Wild boars have been reported as bioindicators for per- and polyfluoroalkyl substances (PFAS) in a variety of studies. However, data about PFAS levels in wild boars from sites with limited industrial and general human activity is scarce. In this study, wild boar (Sus scrofa) organs from the Bohemian Forest National Park (Czech Republic) were used as bioindicators for PFAS pollution. In this work, 29 livers and 24 kidneys from 30 wild boars (0.5-5 years) were investigated using a fluorine mass balance approach. For this, the samples were measured using high performance liquid chromatography with electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS), targeting 30 PFAS, including legacy and replacement PFAS, direct total oxidisable precursor assay (dTOPA) and combustion ion chromatography (CIC). Perfluorocarboxylic acids (PFCAs) from C7 to C14 and perfluorooctanesulfonic acid (PFOS) were detected in >50 % of samples. In the livers, PFCAs dominated the profile with median concentrations of 230 μg/kg for perfluorononanoic acid (PFNA) and 75 μg/kg perfluorooctanoic acid (PFOA). PFOA and PFNA concentrations in the livers were one order of magnitude higher than in livers from wild boars caught in rural NE Germany considered as background concentration. PFOS in liver contributed only 30 % to the Σc(PFASTarget) with a median concentration of 170 μg/kg. Kidneys and livers contain an average of 2460 μg F/kg and 6800 μg F/kg extractable organic fluorine (EOF) respectively. Σc(PFASTarget) add up to a maximum of 10 % of the extractable organic fluorine. After oxidisation of the samples, PFOA, PFNA and Σc(PFASdTOPA) increased in livers, but could not explain the EOF. The elevated concentration of PFOA and PFNA may indicate differences in biomagnification for different habitats or an unidentified PFAS source in proximity to the national park.
- Klíčová slova
- CIC, EOF, Kidney, Liver, PFAS, dTOPA,
- MeSH
- bioindikátory MeSH
- fluor analýza MeSH
- fluorokarbony * analýza MeSH
- kapryláty * MeSH
- kyseliny alkansulfonové * analýza MeSH
- látky znečišťující životní prostředí * analýza MeSH
- lesy MeSH
- lidé MeSH
- mastné kyseliny * MeSH
- prasata MeSH
- Sus scrofa MeSH
- tandemová hmotnostní spektrometrie MeSH
- veřejné parky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bioindikátory MeSH
- fluor MeSH
- fluorokarbony * MeSH
- kapryláty * MeSH
- kyseliny alkansulfonové * MeSH
- látky znečišťující životní prostředí * MeSH
- mastné kyseliny * MeSH
- perfluoro-n-nonanoic acid MeSH Prohlížeč
- perfluorooctane sulfonic acid MeSH Prohlížeč
- perfluorooctanoic acid MeSH Prohlížeč
The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.
- MeSH
- difrakce rentgenového záření MeSH
- fluor * MeSH
- maloúhlový rozptyl MeSH
- micely * MeSH
- polymery MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluor * MeSH
- micely * MeSH
- polymery MeSH
We developed a multifunctional polymer coating for nanoparticles (NPs) that enables simultaneous detection by 19F MRI and shielding from blood plasma fouling. The coating is based on a water-soluble fluorinated poly(N-(2-fluoroethyl)acrylamide) (PFEAM) that shows high 19F MRI sensitivity, cytocompatibility and excellent antifouling properties, significantly outperforming polyethylene glycol. A proof-of-concept experiment was performed by synthesizing polymer-coated gold NPs that were successfully visualized by 19F MRI at magnetic fields close to the fields used in clinical practice. This universal approach can be used for coating and tracing of various NPs upon suitable polymer chain-end modification.
- MeSH
- akrylové pryskyřice chemie farmakologie MeSH
- biokompatibilní potahované materiály chemie farmakologie MeSH
- bioznečištění prevence a kontrola MeSH
- fluor MeSH
- halogenace MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- nanostruktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrylové pryskyřice MeSH
- biokompatibilní potahované materiály MeSH
- fluor MeSH
- polyacrylamide MeSH Prohlížeč
Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.
- Klíčová slova
- (19)F magnetic resonance imaging, Double-stimuli responsivity, Polymer implant, Tunable dissolution,
- MeSH
- fluor MeSH
- krysa rodu Rattus MeSH
- magnetická rezonanční tomografie * MeSH
- polymery * MeSH
- rozpustnost MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluor MeSH
- polymery * MeSH
A straightforward methodology of fluorine substitution by tritium/deuterium is reported. The described method is selective towards the F─C (sp3 ) group and leaves both the aromatic F─C (sp2 ) and F2 ─C (sp3 ) moieties unaffected. Alkylfluorides, readily synthesized from appropriate alcohols by treatment with diethylaminosulfur trifluoride (DAST) reagent in an overall yield up to 76%, undergoes activation with the boron-based Lewis acid B(C6 F5 )3 , and stoichiometric in situ reduction with a tritide/deuteride reagent-the [TMP2(3) H][2(3) HB(C6 F5 )3 ] system of frustrated Lewis pair. This methodology provides an isolated yield of up to 93% of regio-specifically labeled small organic compounds with superior 2 H-enrichment of over 95%. The specific activity of prepared 1-(2-[3 H]-ethyl)naphthalene was determined at 29.0 Ci/mmol. The site selectivity of the Lewis acid/ [TMP2(3) H][2(3) HB(C6 F5 )3 ] approach is orthogonal to currently used methods and allows for isotopic labeling of complementary positions in molecules. Reported labeling methodology proceeds well at ultra-mild reaction conditions (220 mbar of T2 ), allowing very low consumption of the radioactive source (4.2 Ci/156 GBq), and producing limited amount of radioactive waste.
- Klíčová slova
- C─F activation, deuterium labeled alkane, deuterodefluorination, frustrated Lewis pairs, hydrogen activation, non-metallic reagent, tritiodefluorination, tritium labeled alkane, ultra-mild reaction conditions, very low tritium pressure,
- MeSH
- alkylace MeSH
- fluor chemie MeSH
- halogenace * MeSH
- izotopové značení MeSH
- oxidace-redukce MeSH
- tritium chemie MeSH
- uhlík chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluor MeSH
- tritium MeSH
- uhlík MeSH
