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BioMed Research International 2013The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration...
The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, (99m)Tc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs.
Topics: Amikacin; Animals; Drug Administration Routes; Lipids; Lung; Male; Nanoparticles; Particle Size; Radionuclide Imaging; Rats; Rats, Wistar; Technetium; Tissue Distribution
PubMed: 23984315
DOI: 10.1155/2013/136859 -
Journal of Nuclear Cardiology :... Jun 2015
Topics: Coronary Artery Disease; Female; Humans; Male; Myocardial Perfusion Imaging; Technetium; Tomography, Emission-Computed, Single-Photon
PubMed: 25832984
DOI: 10.1007/s12350-015-0122-7 -
Molecules (Basel, Switzerland) Jan 2022Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. Ga-labeled FAP inhibitors based on the cyanopyrrolidine...
Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the Tc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (Tc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl for labeling with Tc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand ( = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, H-NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The Tc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the Tc-iFAP.
Topics: Animals; Endopeptidases; Hep G2 Cells; Humans; Liver Neoplasms, Experimental; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Organotechnetium Compounds; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography; Technetium
PubMed: 35011496
DOI: 10.3390/molecules27010264 -
Dalton Transactions (Cambridge, England... May 2014A versatile strategy to prepare fac-[M(I)(CO)3](+) and cis-[M(I)(CO)2](+) (M = Re, (99m)Tc) complexes was developed using Huisgen click chemistry and monodentate...
A versatile strategy to prepare fac-[M(I)(CO)3](+) and cis-[M(I)(CO)2](+) (M = Re, (99m)Tc) complexes was developed using Huisgen click chemistry and monodentate phosphine ligands to readily incorporate biomolecules and tailor the chemical properties.
Topics: Click Chemistry; Coordination Complexes; Crystallography, X-Ray; Ligands; Molecular Conformation; Phosphines; Rhenium; Technetium
PubMed: 24710681
DOI: 10.1039/c4dt00684d -
European Journal of Hospital Pharmacy :... May 2023Technetium-99m mercapto-acetyl-triglycine ([Tc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological...
OBJECTIVES
Technetium-99m mercapto-acetyl-triglycine ([Tc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological and urological disorders. Patient safety and reliability of this imaging procedure especially depend on the radiochemical purity (RCP) of the [Tc]Tc-MAG3 preparation. Recently, the Summary of Product Characteristics (SPC) of NephroMAG, a kit dedicated to [Tc]Tc-MAG3 preparation, proposed a two-strip thin layer chromatography (TLC) based quality control (QC) method. Also, Straub recently proposed another TLC based QC method. We sought to evaluate the transferability of these QC methods in our hospital radiopharmacy and compared them to our currently employed TLC method and radio-HPLC (high-pressure liquid chromatography) to select the most appropriate in the context of hospital radiopharmacy.
METHODS
Ten consecutive [Tc]Tc-MAG3 preparations were controlled using: HPLC combined with a radiodetector (radio-HPLC), a single strip TLC method (method 1) in current use in our centre, a two-strip TLC method described in the SPC (method SPC) and a two-strip TLC method (method 2) described by Straub . Quantitative results for the four tested QC methods were measured and compared in terms of RCP (%), sodium pertechnetate ([Tc]TcO ) (%) and duration of analysis (min).
RESULTS
RCP was significantly different between method SPC and radio-HPLC (p<0.001) and method 2 (p<0.001). Also, the percentage of [Tc]TcO was statistically different between the radio-HPLC and the method SPC (p<0.001), but not with the method 1 and method 2 group (p>0.05). The duration of analysis (min) was significantly different between the four QC procedures (p<0.001) with method 2 and method SPC being the quickest.
CONCLUSIONS
Our study showed it is possible to transfer and select a quick and reliable QC method for the preparation of NephroMAG kits in our centre. We therefore advise the widespread use of the method from Straub in hospital radiopharmacies.
Topics: Humans; Technetium Tc 99m Mertiatide; Technetium; Reproducibility of Results; Radiopharmaceuticals; Quality Control
PubMed: 34285112
DOI: 10.1136/ejhpharm-2021-002804 -
Inhalation Toxicology Nov 2009Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled... (Comparative Study)
Comparative Study
Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled ultrafine particles are able to translocate into the bloodstream in humans. However, their conclusions were conflicting. We developed a physiologically based kinetic model for (99m)technetium-labelled carbon nanoparticles (Technegas). The model was designed to analyse imaging data. It includes different translocation rates and kinetics for free technetium, and small and large technetium-labelled particles. It was calibrated with data from an experiment designed to assess the fate of nanoparticles in humans after inhalation of Technegas. The data provided time courses of radioactivity in the liver, stomach, urine, and blood. Parameter estimation was performed in a Bayesian context with Markov chain Monte Carlo (MCMC) techniques. Our analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about twofold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation resulted in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement.
Topics: Adult; Bayes Theorem; Carbon; Humans; Inhalation Exposure; Male; Middle Aged; Models, Biological; Models, Chemical; Monte Carlo Method; Nanoparticles; Particle Size; Staining and Labeling; Technetium; Tissue Distribution; Young Adult
PubMed: 19814607
DOI: 10.3109/08958370902748542 -
Journal of Hazardous Materials Feb 2019Iron nanoparticles are a promising new technology to treat contaminated groundwater, particularly as they can be engineered to optimise their transport properties....
Iron nanoparticles are a promising new technology to treat contaminated groundwater, particularly as they can be engineered to optimise their transport properties. Technetium is a common contaminant at nuclear sites and can be reductively scavenged from groundwater by iron(II). Here we investigated the potential for a range of optimised iron nanoparticles to remove technetium from contaminated groundwater, and groundwater/sediment systems. Nano zero-valent iron and Carbo-iron stimulated the development of anoxic conditions while generating Fe(II) which reduced soluble Tc(VII) to sparingly soluble Tc(IV). Similar results were observed for Fe(II)-bearing biomagnetite, albeit at a slower rate. Tc(VII) remained in solution in the presence of the Fe(III) mineral nano-goethite, until acetate was added to stimulate microbial Fe(III)-reduction after which Tc(VII) concentrations decreased concomitant with Fe(II) ingrowth. The addition of iron nanoparticles to sediment microcosms caused an increase in the relative abundance of Firmicutes, consistent with fermentative/anoxic metabolisms. Residual bacteria from the synthesis of the biomagnetite nanoparticles were out-competed by the sediment microbial community. Overall the results showed that iron nanoparticles were highly effective in removing Tc(VII) from groundwater in sediment systems, and generated sustained anoxic conditions via the stimulation of beneficial microbial processes including Fe(III)-reduction and sulfate reduction.
Topics: Geologic Sediments; Groundwater; Iron; Metal Nanoparticles; Microbiota; Phylogeny; Technetium; Water Pollutants, Chemical
PubMed: 30343175
DOI: 10.1016/j.jhazmat.2018.10.008 -
Theranostics 2018Treatment of advanced heart failure with implantable LVADs is increasing, driven by profound unmet patient need despite potential serious complications: bleeding,...
Treatment of advanced heart failure with implantable LVADs is increasing, driven by profound unmet patient need despite potential serious complications: bleeding, infection, and thrombus. The experimental objective was to develop a sensitive imaging approach to assess early thrombus accumulation in LVADs under operational high flow and high shear rates. : A monomeric bifunctional ligand with a fibrin-specific peptide, a short spacer, and Tc chelating amino acid sequence (F1A) was developed and compared to its tetrameric PEG analogue (F4A). Tc attenuation by LVAD titanium (1 mm) was 23%. Tc-F1A affinity to fibrin was K ~10 µM, whereas, the bound Tc-F4A probe was not displaced by F1A (120,000:1). Human plasma interfered with Tc-F1A binding to fibrin clot (p<0.05) in vitro, whereas, Tc-F4A targeting was unaffected. The pharmacokinetic half-life of Tc-F4A was 28% faster (124±41 min) than Tc-F1A (176±26 min) with both being bioeliminated through the urinary system with negligible liver or spleen biodistribution. In mice with carotid thrombus, Tc-F4A binding to the injured carotid was much greater (16.3±3.3 %ID/g, p=0.01) than that measured with an irrelevant negative control, Tc-I4A (3.4±1.6 %ID/g). In an LVAD mock flow-loop (1:1, PBS:human plasma:heparin) operating at maximal flow rate, Tc-F4A bound well to phantom clots in 2 min (p<0.05), whereas Tc-F1A had negligible targeting. Excised LVADs from patients undergoing pump exchange or heart transplant were rewired, studied in the mock flow loop, and found to have spatially variable fibrin accumulations in the inlet and outlet cannulas and bearings. Tc-F4A is a high-avidity prototype probe for characterizing thrombus in LVADs that is anticipated to help optimize anticoagulation, reduce thromboembolic events, and minimize pump exchange.
Topics: Animals; Fibrin; Half-Life; Heart Failure; Heart-Assist Devices; Humans; Mice; Protein Binding; Recombinant Proteins; Staining and Labeling; Technetium; Thrombosis
PubMed: 29464007
DOI: 10.7150/thno.20271 -
Molecular Imaging and Biology Apr 2018Contrast-enhanced ultrasound plays an expanding role in oncology, but its applicability to molecular imaging is hindered by a lack of nanoscale contrast agents that can...
PURPOSE
Contrast-enhanced ultrasound plays an expanding role in oncology, but its applicability to molecular imaging is hindered by a lack of nanoscale contrast agents that can reach targets outside the vasculature. Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting. The purpose of the present study is to determine the quantitative biodistribution of GVs, which is critical for their development as imaging agents.
PROCEDURES
We use a novel bioorthogonal radiolabeling strategy to prepare technetium-99m-radiolabeled ([Tc])GVs in high radiochemical purity. We use single photon emission computed tomography (SPECT) and tissue counting to quantitatively assess GV biodistribution in mice.
RESULTS
Twenty minutes following administration to mice, the SPECT biodistribution shows that 84 % of [Tc]GVs are taken up by the reticuloendothelial system (RES) and 13 % are found in the gall bladder and duodenum. Quantitative tissue counting shows that the uptake (mean ± SEM % of injected dose/organ) is 0.6 ± 0.2 for the gall bladder, 46.2 ± 3.1 for the liver, 1.91 ± 0.16 for the lungs, and 1.3 ± 0.3 for the spleen. Fluorescence imaging confirmed the presence of GVs in RES.
CONCLUSIONS
These results provide essential information for the development of GVs as targeted nanoscale imaging agents for ultrasound.
Topics: Acoustics; Animals; Female; Fluorescence; Imaging, Three-Dimensional; Liver; Mice; Nanostructures; Proteins; Radiopharmaceuticals; Spleen; Technetium; Tissue Distribution; Tomography, Emission-Computed, Single-Photon
PubMed: 28956265
DOI: 10.1007/s11307-017-1122-6 -
Journal of Visualized Experiments : JoVE Dec 2015Recent advances in the application of bone marrow mesenchymal stem cells (BMMSC) for the treatment of tendon and ligament injuries in the horse suggest improved outcome...
Recent advances in the application of bone marrow mesenchymal stem cells (BMMSC) for the treatment of tendon and ligament injuries in the horse suggest improved outcome measures in both experimental and clinical studies. Although the BMMSC are implanted into the tendon lesion in large numbers (usually 10 - 20 million cells), only a relatively small number survive (<10%) although these can persist for up to 5 months after implantation. This appears to be a common observation in other species where BMMSC have been implanted into other tissues and it is important to understand when this loss occurs, how many survive the initial implantation process and whether the cells are cleared into other organs. Tracking the fate of the cells can be achieved by radiolabeling the BMMSC prior to implantation which allows non-invasive in vivo imaging of cell location and quantification of cell numbers. This protocol describes a cell labeling procedure that uses Technetium-99m (Tc-99m), and tracking of these cells following implantation into injured flexor tendons in horses. Tc-99m is a short-lived (t1/2 of 6.01 hr) isotope that emits gamma rays and can be internalized by cells in the presence of the lipophilic compound hexamethylpropyleneamine oxime (HMPAO). These properties make it ideal for use in nuclear medicine clinics for the diagnosis of many different diseases. The fate of the labeled cells can be followed in the short term (up to 36 hr) by gamma scintigraphy to quantify both the number of cells retained in the lesion and distribution of the cells into lungs, thyroid and other organs. This technique is adapted from the labeling of blood leukocytes and could be utilized to image implanted BMMSC in other organs.
Topics: Animals; Bone Marrow Cells; Horse Diseases; Horses; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Radionuclide Imaging; Technetium; Tendinopathy; Tendons
PubMed: 26709915
DOI: 10.3791/52748