scholarly journals New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2373
Author(s):  
Jordi Borràs ◽  
Julie Foster ◽  
Roxana Kashani ◽  
Laura Meléndez-Alafort ◽  
Jane Sosabowski ◽  
...  
Keyword(s):  
Folic Acid ◽  
Specific Binding ◽  
Zinc Complexes ◽  
In Vivo Studies ◽  
Reaction Yield ◽  
Water Medium ◽  
One Pot ◽  
Molar Activity ◽  
High Yields

The zinc dithiocarbamates functionalized with folic acid 2Zn and 3Zn were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (1Zn). Zinc complexes 2Zn and 3Zn show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes 2Zn or 3Zn and the cation fac-[99mTc(H2O)3(CO)3]+, in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac-[99mTc(CO)3(SS)(P)] bioconjugated to folic acid (2Tc and 3Tc). In spite of the low solubility of 2Zn and 3Zn in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes (2Re and 3Re) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2Tc and 3Tc indicate low specific binding to folate receptors. In summary, Tc-99m folates 2Tc and 3Tc were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

scholarly journals A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Ksenia Lisova ◽  
Jia Wang ◽  
Philip H. Chao ◽  
R. Michael van Dam
Keyword(s):  
Large Scale ◽  
Solid Phase ◽  
Acetonitrile Solution ◽  
Synthesis Methods ◽  
Pet Tracers ◽  
Molar Activity ◽  
Alternative Approaches ◽  
High Yields ◽  
Sufficient Concentration

Abstract Background Current automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [18F]Florbetaben for use in imaging of Alzheimer’s disease. Procedures The microscale synthesis of [18F]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [18F]fluoride was azeotropically dried with K2CO3/K222 (275/383 nmol) complex prior to radiofluorination of the Boc-protected precursor (80 nmol) in 10 μL DMSO at 130 °C for 5 min. The resulting intermediate was deprotected with HCl at 90 °C for 3 min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge. Results Starting with 270 ± 100 MBq (n = 3) of [18F]Fluoride, the method affords formulated product with 49 ± 3% (decay-corrected) yield,> 98% radiochemical purity and a molar activity of 338 ± 55 GBq/μmol. The miniature C18 cartridge enables efficient elution with only 150 μL of ethanol which is diluted to a final volume of 1.0 mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55 min. Conclusions This work describes an efficient and reliable procedure to produce [18F]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention.

scholarly journals Antibacterial and In Vivo Studies of a Green, One-Pot Preparation of Copper/Zinc Oxide Nanoparticle-Coated Bandages

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 462
Author(s):  
Archana R. Deokar ◽  
Ilana Perelshtein ◽  
Melissa Saibene ◽  
Nina Perkas ◽  
Paride Mantecca ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Metal Oxide ◽  
Ultrasound Irradiation ◽  
Face Mask ◽  
In Vivo Studies ◽  
One Pot ◽  
The Face ◽  
Bulk Scale ◽  
Particle Size And Shape

Simultaneous water and ethanol-based synthesis and coating of copper and zinc oxide (CuO/ZnO) nanoparticles (NPs) on bandages was carried out by ultrasound irradiation. High resolution-transmission electron microscopy demonstrated the effects of the solvent on the particle size and shape of metal oxide NPs. An antibacterial activity study of metal-oxide-coated bandages was carried out against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). CuO NP-coated bandages made from both water and ethanol demonstrated complete killing of S. aureus and E. coli bacteria within 30 min., whereas ZnO NP-coated bandages demonstrated five-log reductions in viability for both kinds of bacteria after 60 min of interaction. Further, the antibacterial mechanism of CuO/ZnO NP-coated bandages is proposed here based on electron spin resonance studies. Nanotoxicology investigations were conducted via in vivo examinations of the effect of the metal-oxide bandages on frog embryos (teratogenesis assay—Xenopus). The results show that water-based coatings resulted in lesser impacts on embryo development than the ethanol-based ones. These bandages should therefore be considered safer than the ethanol-based ones. The comparison between the toxicity of the metal oxide NPs prepared in water and ethanol is of great importance, because water will replace ethanol for bulk scale synthesis of metal oxide NPs in commercial companies to avoid further ignition problems. The novelty and importance of this manuscript is avoiding the ethanol in the typical water:ethanol mixture as the solvent for the preparation of metal oxide NPs. Ethanol is ignitable, and commercial companies are trying the evade its use. This is especially important these days, as the face mask produced by sonochemistry (SONOMASK) is being sold all over the world by SONOVIA, and it is coated with ZnO.

scholarly journals One-pot multi-component process for the synthesis of 4-azaphenanthrene-3,10-dione, 1,8-dioxo-octahydroxanthene and tetrahydrobenzo[b]pyran derivatives catalyzed by the deep eutectic solvent choline chloride-oxalic acid

2020 ◽  
Vol 75 (3) ◽  
pp. 269-279
Author(s):  
Mohammad Hosein Sayahi ◽  
Maryam Gorjizadeh ◽  
Melan Meheiseni ◽  
Soheil Sayyahi
Keyword(s):  
Oxalic Acid ◽  
Choline Chloride ◽  
Deep Eutectic Solvent ◽  
Reaction Times ◽  
Eutectic Mixture ◽  
Reaction Yield ◽  
One Pot ◽  
Experimental Procedure ◽  
Component Process ◽  
High Yields

AbstractAn effective method based on choline chloride (ChCl)-oxalic acid (Ox) deep eutectic solvent was proposed for the synthesis of 4-azaphenanthrene-3,10-dione, 1,8-dioxo-octahydroxanthene and tetrahydrobenzo[b]pyran derivatives. The eutectic mixture worked as both the solvent and acidic catalyst for conversion. The impacts of different variables, including the composition and volume of ChCl-Ox, and temperature, on reaction yield were studied for optimization. The crucial advantages of this process are simplicity of the experimental procedure, high yields, short reaction times, high recyclability, and the use of safe and inexpensive components.

Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo

2017 ◽  
Vol 8 (6) ◽  
pp. 1104-1113 ◽  
Author(s):  
Yi Cao ◽  
Min Liu ◽  
Guangyue Zu ◽  
Ye Kuang ◽  
Xiaoyan Tong ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Folic Acid ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Resonance Imaging ◽  
One Pot ◽  
Hyperbranched Poly ◽  
T1 Contrast Agent ◽  
T1 Contrast

To explore a convenient and efficient strategy for constructing tumor-targeted T1 mCAs for MRI, hyperbranched poly(glycerol) prepared in one-pot was used to conjugate gadolinium chelates and folic acid ligands through “click chemistry”.

scholarly journals Radiosynthesis and Evaluation of Cyclohexyl (5-(2-[11C-Carbonyl]acetamidobenzo[d]thiazol-6-yl)-2-Methylpyridin-3-yl)Carbamate ([11C]PK68) As a New Radioligand For Imaging Receptor-Interacting Protein 1 Kinase

2022 ◽  
Author(s):  
Tomoteru Yamasaki ◽  
Katsushi Kumata ◽  
Atsuto Hiraishi ◽  
Yiding Zhang ◽  
Hidekatsu Wakizaka ◽  
...  
Keyword(s):  
Acetyl Chloride ◽  
Radiochemical Purity ◽  
Specific Binding ◽  
Small Animal ◽  
Small Animal Pet ◽  
Interacting Protein ◽  
Molar Activity ◽  
Positron Emission ◽  
Key Enzyme

Abstract Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we radiosynthesized [11C]PK68 as a new positron emission tomography (PET) ligand for imaging RIPK1 and evaluated its potential in vivo.Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq (n = 10) with >99% radiochemical purity and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and was subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo, and may be used as a lead compound for further candidate development.Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 and evaluated its potential in vivo. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models.

scholarly journals Nanoformulation of a Novel Pyrano[2,3-c] Pyrazole Heterocyclic Compound AMDPC Exhibits Anti-Cancer Activity via Blocking the Cell Cycle through a P53-Independent Pathway

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 624 ◽  
Author(s):  
Xuanrong Sun ◽  
Longchao Zhang ◽  
Mengshi Gao ◽  
Xiangjie Que ◽  
Chenfeng Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Biological Activities ◽  
Polymeric Micelle ◽  
In Vivo Studies ◽  
One Pot ◽  
Anti Cancer ◽  
G2 Phase ◽  
Anti Tumor Activity

Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of P21 gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed.

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