scholarly journals Introduction of Re(CO)3+/99mTc(CO)3+ Organometallic Species into Vinylpyrrolidone-Allyliminodiacetate Copolymers

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1832
Author(s):  
Nikolay Ivanovich Gorshkov ◽  
Andrei Yur'evich Murko ◽  
Yulia Igorevna Zolotova ◽  
Olga Vladimirovna Nazarova ◽  
Valerii Dmitrievich Krasikov ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Nmr Spectra ◽  
Optimal Conditions ◽  
Mild Conditions ◽  
Polymeric Carriers ◽  
Molecular Masses ◽  
Polymeric Complexes ◽  
Radiochemical Yields ◽  
Polymerization Conditions

N-vinylpyrrolidone-co-allylamine copolymers (VP-co-AA) containing iminodiacetic (IDA) chelation units were prepared in the range of molecular masses of the copolymers from 9000 to 30,000 Da depending on polymerization conditions. Non-radioactive organometallic species Re(CO)3+ were introduced into polymeric carriers under mild conditions; the prepared metal–polymeric complexes were characterized by IR, NMR, ESI-MS and HPLC. IR spectra data confirmed the coordination of M(CO)3+ moiety to the polymeric backbone via IDA chelation unit (appearance of characteristic fac-M(CO)3+ vibrations (2005, 1890 cm−1), as well as the appearance of group of signals in 1H NMR spectra, corresponding to those inequivalent to methylene protons CH2COO (dd, 4.2 ppm), coordinated to metal ions. The optimal conditions for labeling the PVP-co-AA-IDA copolymers with radioactive 99mTc(CO)3+ species were determined. The radiochemical yields reached 97%. The obtained radiolabeled polymers were stable in blood serum for 3 h. In vivo distribution experiments in intact animals showed the high primary accumulation of technetium-99m MPC (MM = 15,000 Da) in blood with subsequent excretion via the urinary tract.

scholarly journals Radiolabeling of Human Serum Albumin With Terbium-161 Using Mild Conditions and Evaluation of in vivo Stability

2021 ◽  
Vol 8 ◽  
Author(s):  
Irwin Cassells ◽  
Stephen Ahenkorah ◽  
Andrew R. Burgoyne ◽  
Michiel Van de Voorde ◽  
Christophe M. Deroose ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
High Yield ◽  
Mild Conditions ◽  
Bifunctional Ligands ◽  
Pharmacokinetic Properties ◽  
Therapeutic Properties ◽  
Radiochemical Yields

Targeted radionuclide therapy (TRNT) is a promising approach for cancer therapy. Terbium has four medically interesting isotopes (149Tb, 152Tb, 155Tb and 161Tb) which span the entire radiopharmaceutical space (TRNT, PET and SPECT imaging). Since the same element is used, accessing the various diagnostic or therapeutic properties without changing radiochemical procedures and pharmacokinetic properties is advantageous. The use of (heat-sensitive) biomolecules as vector molecule with high affinity and selectivity for a certain molecular target is promising. However, mild radiolabeling conditions are required to prevent thermal degradation of the biomolecule. Herein, we report the evaluation of potential bifunctional chelators for Tb-labeling of heat-sensitive biomolecules using human serum albumin (HSA) to assess the in vivo stability of the constructs. p-SCN-Bn-CHX-A”-DTPA, p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA were conjugated to HSA via a lysine coupling method. All HSA-constructs were labeled with [161Tb]TbCl3 at 40°C with radiochemical yields higher than 98%. The radiolabeled constructs were stable in human serum up to 24 h at 37°C. 161Tb-HSA-constructs were injected in mice to evaluate their in vivo stability. Increasing bone accumulation as a function of time was observed for [161Tb]TbCl3 and [161Tb]Tb-DTPA-CHX-A”-Bn-HSA, while negligible bone uptake was observed with the DOTA, DOTA-GA and NETA variants over a 7-day period. The results indicate that the p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA are suitable bifunctional ligands for Tb-based radiopharmaceuticals, allowing for high yield radiolabeling in mild conditions.

Application of Poly(Vinylbenzyltrimethylammonium Tribromide) Resin as an Efficient Polymeric Catalyst in the Acetalization and Diacetylation of Benzaldehydes

2020 ◽  
Vol 17 ◽  
Author(s):  
Zubiao Zheng ◽  
Bingbing Han ◽  
Junjun Hu ◽  
Xianwei Li
Keyword(s):  
High Efficiency ◽  
Optimal Conditions ◽  
Mild Conditions ◽  
Polymeric Catalyst

: The applications of a new supported tribromide reagent (poly(vinylbenzyltrimethylammonium tribromide) resin) were reported. This supported tribromide resin was used as a catalyst in the acetalization and diacetylation of benzaldehydes under mild conditions with high efficiency. The effects of solvents, amount of the supported tribromide resin on the reactions were investigated. Under the optimal conditions, most of acetal and 1,1-diacetates of benzaldehydes were selectively obtained in excellent yields.

scholarly journals Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Klaudia A. Cybulska ◽  
Vera Bloemers ◽  
Lars R. Perk ◽  
Peter Laverman
Keyword(s):  
Significant Degree ◽  
Translocator Protein ◽  
Positron Emission ◽  
Leaving Group ◽  
Inflammatory Processes ◽  
Single Production ◽  
Translocator Protein 18 Kda ◽  
Radiochemical Yields ◽  
Specific Ligand

Abstract Background The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. Results [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. Conclusion To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

scholarly journals Simplified 89Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1097
Author(s):  
Andras Polyak ◽  
Jens P. Bankstahl ◽  
Karen F. W. Besecke ◽  
Constantin Hozsa ◽  
Wiebke Triebert ◽  
...  
Keyword(s):  
Reaction Times ◽  
Extraction Methods ◽  
Cell Labeling ◽  
Size Exclusion ◽  
Cell Therapies ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Human Ipscs ◽  
Radiochemical Yields

In this work, a method for the preparation of the highly lipophilic labeling synthon [89Zr]Zr(oxinate)4 was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [89Zr]Zr(oxinate)4 was prepared from oxine (8-hydroxyquinoline) and [89Zr]Zr(OH)2(C2O4). Earlier introduced liquid–liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the 89Zr-complex was incorporated into liposome formulations. PET/CT imaging of 89Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 106 hiPSCs, each. [89Zr]Zr(oxinate)4 was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [89Zr]Zr(oxinate)4 into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers’ in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible 89Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.

scholarly journals degS Is Necessary for Virulence and Is among Extraintestinal Escherichia coli Genes Induced in Murine Peritonitis

2003 ◽  
Vol 71 (6) ◽  
pp. 3088-3096 ◽  
Author(s):  
Peter Redford ◽  
Paula L. Roesch ◽  
Rodney A. Welch
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Luria Bertani ◽  
Broth Culture ◽  
Wild Type ◽  
E Coli ◽  
Virulence Attenuation

ABSTRACT Extraintestinal Escherichia coli strains cause meningitis, sepsis, urinary tract infection, and other infections outside the bowel. We examined here extraintestinal E. coli strain CFT073 by differential fluorescence induction. Pools of CFT073 clones carrying a CFT073 genomic fragment library in a promoterless gfp vector were inoculated intraperitoneally into mice; bacteria were recovered by lavage 6 h later and then subjected to fluorescence-activated cell sorting. Eleven promoters were found to be active in the mouse but not in Luria-Bertani (LB) broth culture. Three are linked to genes for enterobactin, aerobactin, and yersiniabactin. Three others are linked to the metabolic genes metA, gltB, and sucA, and another was linked to iha, a possible adhesin. Three lie before open reading frames of unknown function. One promoter is associated with degS, an inner membrane protease. Mutants of the in vivo-induced loci were tested in competition with the wild type in mouse peritonitis. Of the mutants tested, only CFT073 degS was found to be attenuated in peritoneal and in urinary tract infection, with virulence restored by complementation. CFT073 degS shows growth similar to that of the wild type at 37°C but is impaired at 43°C or in 3% ethanol LB broth at 37°C. Compared to the wild type, the mutant shows similar serum survival, motility, hemolysis, erythrocyte agglutination, and tolerance to oxidative stress. It also has the same lipopolysaccharide appearance on a silver-stained gel. The basis for the virulence attenuation is unclear, but because DegS is needed for σE activity, our findings implicate σE and its regulon in E. coli extraintestinal pathogenesis.

scholarly journals Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

2007 ◽  
Vol 57 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Savita Vyas ◽  
Piyush Trivedi ◽  
Subhash Chaturvedi
Keyword(s):  
Human Plasma ◽  
Parent Drug ◽  
Aqueous Solubility ◽  
Spectrophotometric Analysis ◽  
In Vivo Evaluation ◽  
Gastrointestinal Side Effects ◽  
Molecular Masses ◽  
Anti Inflammatory

Ketorolac-dextran conjugates: Synthesis,in vitroandin vivoevaluationKetorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. Invitrohydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics.In vivobiological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

BSA directed-synthesis of biocompatible Fe3O4 nanoparticles for dual-modal T1 and T2 MR imaging in vivo

2017 ◽  
Vol 9 (21) ◽  
pp. 3099-3104 ◽  
Author(s):  
Dong Li ◽  
Minghui Hua ◽  
Kun Fang ◽  
Rong Liang
Keyword(s):  
Bovine Serum Albumin ◽  
Mr Imaging ◽  
Serum Albumin ◽  
Fe3o4 Nanoparticles ◽  
Bovine Serum ◽  
Mild Conditions ◽  
Directed Synthesis ◽  
T1 And T2

Bovine serum albumin-Fe3O4 nanoparticles with undoubted biosafety and robust dual-modal T1 and T2 MR imaging ability were fabricated using a biomineralization approach in a facile way under mild conditions for in vivo MR imaging.

Update on the Treatment of Bacterial Urinary Tract Infections

1981 ◽  
Vol 15 (10) ◽  
pp. 738-750 ◽  
Author(s):  
Neil Massoud
Keyword(s):  
Biological Activity ◽  
Single Dose ◽  
Urinary Tract ◽  
Patient Compliance ◽  
Urinary Tract Infections ◽  
Antimicrobial Agents ◽  
Complex Problem ◽  
Tract Infections

The treatment of urinary tract infections (UTIs) has become a complex problem for the clinical practitioner. An understanding of the pharmacology, pharmacokinetics, and in vivo biological activity of antimicrobial agents is needed, as is an understanding of the variables that may influence patient compliance with medication regimens. Although UTIs are usually treated for 10 to 14 days, shorter treatment schedules of seven to ten days or even single-dose regimens are possible. Guidelines for the treatment of UTIs are presented along with suggestions for increased patient compliance.

Magnetic resonance imaging (1H) and spectroscopy (1H, 31P) of growing chicken embryos

1993 ◽  
Vol 73 (4) ◽  
pp. 953-965 ◽  
Author(s):  
A. Lirette ◽  
Z. Liu ◽  
D. C. Crober ◽  
R. A. Towner ◽  
U. M. Oehler ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Magnetic Resonance ◽  
Nmr Spectra ◽  
Surface Coil ◽  
Nmr Imaging ◽  
Chicken Embryos ◽  
H Nmr ◽  
Imaging And Spectroscopy ◽  
Two Peaks

Nuclear magnetic resonance (NMR) imaging and spectroscopy techniques were used to observe in vivo anatomical and metabolite changes, respectively, in developing chicken embryos. Proton (1H) NMR images of the eggs revealed major changes in yolk shape from day 2 to day 6. Embryos were visible from day 6 to hatching, and good embryonic anatomical images were obtained. Two peaks were observed from 1H-NMR spectroscopy of fertilized eggs: one for lipid methylene protons, and one for water protons. Water peak to lipid peak ratios did not vary significantly (P > 0.05) from day 2 to day 21 of incubation. Localized 31P-NMR spectra of developing embryos were obtained with either a 31P surface coil or a double-tuned 31P/1H volume coil. The surface-coil method gave a greater signal to noise ratio by a factor of four. The 31P-NMR spectra indicated two peaks at day 2; these were attributed to phosphomonoesters and phosphodiesters. The three peaks characteristic of ATP appeared on day 11 and increased in size until hatching. From day 19, phosphocreatine was detectable. There appeared to be a good correlation between 31P-metabolite changes detected by in vivo 31P-NMR spectroscopy and literature values for biochemical analyses of developing chicken embryos. The advantage in using NMR imaging and spectroscopy techniques is that anatomical and metabolic changes can be obtained in vivo, non-invasively and repeatedly as an embryo develops. Key words: NMR, MRI, embryo, poultry

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