Novel Gd-DTPA-peptide for targeted breast tumor magnetic resonance imaging.

The prevalence of breast cancer underscores the imperative for early diagnosis in guiding treatment decisions. This study introduces a novel contrast agent, Gd-DTPA-VGB3, derived from the peptide VGB3 targeting vascular endothelial growth factor receptor-1 (VEGFR1) and VEGFR2, to enhance the contrast of conventional drug Magnevist in breast tumor MRI. The MRI contrast agent was synthesized on rink amide resin via Fmoc strategy, incorporating amino acids, and coupling to diethylenetriaminepentaacetic acid (DTPA). Gadolinium (Gd)-DTPA-VGB3 displayed specific binding to VEGFR1/2 in a displacement binding assay. Gd-DTPA-VGB3 exhibited minimal cytotoxicity to normal MCF-10 cells while inhibiting 4T1 mammary carcinoma cell proliferation. Compared to Magnevist, Gd-DTPA-VGB3 demonstrated a 2.8-fold increase in contrast-to-noise ratio (CNR) (355 vs. 125). Gd-DTPA-VGB3 exhibited enhanced accumulation in 4T1 tumor-bearing mice, resulting in significant signal intensity improvement. The findings highlight Gd-DTPA-VGB3's specific binding to VEGFRs, substantiating its potential as a candidate for enhancing MRI contrast in breast cancer diagnostics.

Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer.

As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient's chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression.

Characterization of a novel TiF4 inclusion complex and its in vitro evaluation on inhibiting enamel demineralization.

Titanium tetrafluoride (TiF4) is an anticariogenic agent with high remineralizing potential. However, the acidic pH of TiF4 solution can limit its clinical application. Dendrimers have been reported to show promising remineralizing potentials. Thus, the present study aimed to prepare and characterize a new TiF4 dendrimer inclusion complex and evaluate its ability to inhibit enamel demineralization under pH cycling conditions. PEG-citrate dendrimer and TiF4-dendrimer inclusion complex were synthesized and their molecular structures were evaluated using FTIR, H NMR, and LC-MS tests. Forty-eight enamel samples were prepared randomly and divided into four groups: distilled water (negative control), TiF4 solution (T), dendrimer solution (D), and TiF4-dendrimer solution (TD). The microhardness of the samples was measured initially. Next, the samples underwent pH-cycling, were exposed to the solutions, the microhardness was measured again, and microhardness loss was calculated. EDX analysis was performed on the surface and cross-sectional segments of the samples. The microhardness loss was significantly higher in control (-65.1± 6.0) compared to other groups. No significant difference was observed between T (-47.9± 5.6) and D (-41.7± 12.0), and also D and TD (-40.5± 9.4) in this regard. Microhardness loss was significantly higher in T compared to TD group. The T+D samples showed similar fluoride and titanium content in both surface and subsurface regions, while the T group had higher concentrations in the surface region. Moreover, the DT solution had a higher pH of 3.4 compared to the T solution's pH of 1.1. TiF4-dendrimer solution showed similar efficacy in inhibiting demineralization comparable to TiF4 solution, with the added advantage of having a higher pH.

Effervescent tablet-assisted deep eutectic solvent based on magnetic nanofluid for liquid phase microextraction of tyrosine kinase inhibitors in plasma samples by high-performance liquid chromatography.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are efficient anti-cancer drugs. The analysis of TKIs in the treatment of cancer is important to achieve the highest anti-cancer effects with minimal toxicities. Herein, we report an efficient effervescent tablet-assisted deep eutectic solvent based on nanofluid (ETA-DES-NF) combined with HPLC-UV for the determination of three anti-cancer drugs (erlotinib, imatinib, and nilotinib) in human plasma samples. METHODS: In this method, a magnetic nanofluid composed of deep eutectic solvent (DES) and Fe3O4@SiO2 nanoparticles was used as an extraction solvent. The deep eutectic solvent acted as a carrier and stabilizer for Fe3O4@SiO2 nanoparticles. A tablet was used in the nanofluid for dispersion. The effervescent tablet was implemented to generate in situ CO2 and provide the effective dispersion of the sorbent into the sample solution for diminishing the extraction time and improving the extraction efficiency. Moreover, the magnetic nanofluid enhanced phase separation efficiency without centrifugation to collect the organic solvent. RESULTS: The synthesized nanofluid was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and vibrating sample magnetometry (VSM). The impact of main parameters, including the type and volume of DES, the composition of the tablet, the composition of the nanofluid and the composition of eluent, were optimized. According to the optimized conditions, the limits of detection (LODs) and the limits of quantitation (LOQs) were from 0.5-0.8 to 1.5-2.4 µg L-1 for imatinib, erlotinib, and nilotinib, respectively. The intra-day and inter-day relative standard deviations (RSD% n = 5) were determined to be 3.1-5% and 6.4-7.5%, respectively. CONCLUSIONS: The developed method displayed high sensitivity, low consumption of solvent, low cost, simplicity, high recoveries, short extraction time, and good repeatability for determination of three anti-cancer drugs in human plasma samples.

Separation and quantification of diazinon in water samples using liquid-phase microextraction-based effervescent tablet-assisted switchable solvent method coupled to gas chromatography-flame ionization detection.

This study used a liquid-phase microextraction-based effervescent tablet-assisted switchable solvent method coupled to gas chromatography-flame ionization detection as an eco-efficient, convenient-to-use, cost-effective, sensitive, rapid, and efficient method for extracting, preconcentrating, and quantifying trace amounts of diazinon in river water samples. As a switchable solvent, triethylamine (TEA) was used. In situ generation of CO2 using effervescent tablet containing Na2 CO3 and citric acid changed the hydrophobic TEA to the hydrophilic protonated triethylamine carbonate (P-TEA-C). CO2 removal from the specimen solution using NaOH caused P-TEA-C to be converted into TEA and led to phase separation, during which diazinon was extracted into the TEA phase. The salting-out process was helpful in enhancing extraction efficiency. In addition, a number of significant parameters that affect extraction recovery were examined. Under optimum conditions, the limit of detection and limit of quantitation were 0.06 and 0.2 ng/ml, respectively. The extraction recovery percentage and pre-concentration factor were obtained at 95 and 190%, respectively, and the precision (inter- and intra-day, relative standard deviation %, n = 5) was <5%.

Deep eutectic solvent as the acceptor phase in three-phase hollow fiber liquid-phase microextraction for the determination of pyrethroid insecticides from environmental water samples prior to HPLC.

In this study, a deep eutectic solvent as the acceptor phase was applied in three-phase hollow fiber liquid-phase microextraction for the microextraction of two pyrethroids (permethrin as well as deltamethrin) from environmental water samples prior to HPLC-UV. A deep eutectic solvent was synthesized of tetrabutylammonium bromide-decanoic acid (in a ratio of 1:2) as an acceptor phase and 1-decanol was applied as a supported liquid membrane. Some main variables affecting the extraction recoveries, comprising the types/contents of extraction solvent and acceptor phase, stirring speed, sample phase pH and extraction time, were checked and optimized. Under optimal conditions, the detection limits and limits of quantitation determined were 0.09-0.12 and 0.29-0.39 µgl-1 for deltamethrin and permethrin, respectively. The enrichment factors were 627 and 613, while the relative standard deviations (n = 5) were 4.8 and 5.7%, for deltamethrin and permethrin, respectively. The created technique was assessed as satisfactory to ascertain the two pyrethroid poisons (permethrin and deltamethrin) in environmental water samples.

Air-assisted in situ deep eutectic solvent decomposition followed by the solidification of floating organic droplets-liquid-liquid microextraction method for extraction of azole antifungal drugs in biological samples prior to high-performance liquid chromatography.

A free dispersive method, air-assisted in situ deep eutectic solvent decomposition followed by the solidification of floating organic droplets liquid-liquid microextraction was indicated in this study. This technique was utilized to simultaneously ascertain some azole antifungal drugs prior to high-performance liquid chromatography. In this research, a quasi-hydrophobic deep eutectic solvent was formed from tetrabutylammonium bromide and 1-dodecanol as an organic solvent at a 1:2 molar ratio. The synthesized deep decomposition in the sample solution caused in situ dispersion of extraction solvent and analytes. Air-assisted enhanced a dispersion condition in the sample solution. 1-Dodecanol as a green option was replaced with typical extraction solvents providing the advantages of a suitable freezing point near room temperature and low density. The effect of important analytical parameters on the extraction recovery of analytes was assessed. Under these optimal conditions, the limits of detection and the limits of quantitation determined were in the range of 0.5-2.8 and 1.5-9 µg/L, for water, urine and plasma samples, respectively. The intra-day and inter-day relative standard deviations (n = 5) were calculated to be 2.9-4.6 and 4.2-8.9%, respectively. The results represented the effectiveness of the developed method for the extraction and determination of analytes in biological samples.

Development of effervescence-assisted switchable polarity solvent homogeneous liquid-phase microextraction for the determination of permethrin and deltamethrin in water samples prior to gas chromatography-flame ionization detection.

An effervescent tablet-assisted switchable polarity solvent-based homogeneous liquid-phase microextraction combined with gas chromatography with flame ionization detection has been conducted for the separation, preconcentration, and detection of permethrin and deltamethrin in the river water specimens. Triethylamine (TEA) was utilized as the switchable polarity solvent in this method. The switching process was carried out by the dissolution of an effervescent tablet including an effervescency agent (sodium carbonate) and a proton donor agent (citric acid). Changing the pH of the specimen solution enhanced the conversion of TEA into protonated triethylamine carbonate through the tablet that generated carbon dioxide bubbles in situ. Finally, the addition of sodium hydroxide changed the ionization state of TEA and separated the two phases. Influential factors in the extraction were investigated. According to optimal situations, the limit of detection and the limit of quantification were 0.16 and 0.5 µg L-1 for permethrin and 0.03 and 0.1 µg L-1 for deltamethrin, respectively. The preconcentration factor was 194 in river water samples and inter- and intra-day precision (relative standard deviation %; n = 5) was <5%. The extraction recovery was obtained in the range of 93.0%-97% for permethrin and deltamethrin in water samples.

Fabrication of an SPME fiber based on ZnO@GA nanorods coated onto fused silica as a highly efficient absorbent for the analysis of cancer VOCs in water and urine.

Analysis of volatile organic compounds (VOCs) secreted in urine, blood, breath, etc. is a new method for monitoring the metabolism and biochemistry of the human body. However, due to the complexity of samples, a pre-concentration step is necessary before the final analysis with gas chromatography-mass spectroscopy (GC-MS). Therefore, miniaturized extraction methods such as solid-phase microextraction (SPME) can be a promising and simple pre-concentration technique. Different strategies have been adopted for the fabrication or modification of SPME fibers. This study presents the preparation and characterization of glass optical fibers coated with ZnO nanorods functionalized with gallic acid (ZnO@GA nanorod) as SPME adsorbent in GC-MS. ZnO@GA nanorods were synthesized separately and then coated onto the fibers. The coated fibers were characterized by using field emission scanning electron microscopy coupled with energy dispersive analysis of X-rays (FESEM/EDAX) and Fourier transform infrared spectroscopy (FTIR) techniques. Possessing a high surface to volume ratio of ZnO nanorods and functional groups of GA, the ZnO@GA nanorod-based SPME fibers exhibited good extraction performance for VOCs comparing with the commercial polydimethylsiloxane (PDMS) coated fibers. Under optimal conditions (NaCl concentration, 30% w/v; extraction time of 25 min; pH, 5-7 and stirring rate of 400 rpm) ZnO@GA nanorods coated fibers achieved low detection limits (0.32-4.8 µg/L), low quantification limits (1.8-16.3 µg/L) and good linearity (5-1000 µg/L) for selected VOCs. The repeatability (n = 3) for a single fiber was within the range of 4.1-7.9% (intra-day) and 5.7-9.6% (inter-day) while the reproducibility (n = 3) of fiber-to-fiber were in the range of 4.7% and 9.9%. This method was successfully used for the determination of six VOCs in water and urine with satisfactory recoveries of 90-112%. ZnO@GA nanorod coated fibers, despite possessing a much thinner coating compared to the commercial fibers, revealed a better overall extraction efficiency towards VOCs. These results indicated that the ZnO@GA provided a promising alternative in sample pretreatment and analysis in GC-MS.

Method development for determination of imatinib and its major metabolite, N-desmethyl imatinib, in biological and environmental samples by SA-SHS-LPME and HPLC.

A salting-out-assisted switchable hydrophilicity solvent-based liquid phase microextraction (SA-SHS-LPME) was developed for the separation and determination of trace amounts of imatinib and N-desmethyl imatinib in biological and environmental samples by HPLC-UV. Triethylamine as a hydrophobic compound and protonated triethylamine carbonate as a hydrophilic one were switched by the addition or elimination of CO2 . The use of NaOH resulted in the elimination of CO2 from the sample solution, which led to the conversion of P-TEA-C into triethylamine (TEA) and as a result, the analytes was extracted and entered the TEA phase. The salting out was performed to speed up the formation of the TEA in the shape of fine droplets in the specimen solution. Furthermore, the impact of several momentous factors that influence the recovery of the extraction was investigated. Under the optimum conditions, the limit of detection and limit of quantification were obtained in ranges of 0.03-0.05 and 0.1-0.15 µg L-1 for imatinib and 0.04-0.06 and 0.13-0.20 µg L-1 for N-desmethyl imatinib, respectively. The preconcentration factor was 250. Inter- and intraday precision (RSD, n = 5) was <5%. In the case of imatinib and N-desmethyl imatinib in biological and environmental specimens, a range of 97.0-102% was obtained as the recovery.

177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study.

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80-85% of death. αvß3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of αvß3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK)2 with 177Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of -3.878 was obtained for 177Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (Kd) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing αvß3 integrin receptors.

Effervescent tablet-assisted demulsified dispersive liquid-liquid microextraction based on solidification of floating organic droplet for determination of methadone in water and biological samples prior to GC-flame ionization and GC-MS.

A novel effervescent tablet-assisted demulsified dispersive liquid-liquid microextraction based on the solidification of floating organic droplet was developed to determine methadone prior to gas chromatography with flame ionization detection and gas chromatography with mass spectrometry. In this method, a tablet composed of citric acid, sodium carbonate, and 1-undecanol was utilized. The resulting effervescent tablet generated carbon dioxide in situ to disperse 1-undecanol in the sample. Thus, the dispersive and extraction processes were performed in one synchronous step. An aliquot of acetonitrile as the demulsifier solvent was used for the separation of two phases instead of centrifugation. Under optimal conditions, the developed method was linear up to 50 000 µg/L with correlation coefficients higher than 0.99. Moreover, limits of detection and limits of the quantification were in the range of 3-10  and 7-30 µg/L in water and biological samples, respectively. Intra- and interday precisions (n = 6) of the spiked methadone at a concentration level of 50 µg/L were over ranges of 5.1-6.8% and 5.7-7.1%, respectively. The preconcentration factors and recovery values were obtained in the range of 140-145 and 98.1 to 101.6% in real samples, respectively.

Radiosynthesis, Biological Evaluation, and Preclinical Study of a 68Ga-Labeled Cyclic RGD Peptide as an Early Diagnostic Agent for Overexpressed α v ß 3 Integrin Receptors in Non-Small-Cell Lung Cancer.

The α v ß 3 integrin receptors have high expression on proliferating growing tumor cells of different origins including non-small-cell lung cancer. RGD-containing peptides target the extracellular domain of integrin receptors. This specific targeting makes these short sequences a suitable nominee for theranostic application. DOTA-E(cRGDfK)2 was radiolabeled with 68Ga efficiently. The in vivo and in vitro stability was examined in different buffer systems. Metabolic stability was assessed in mice urine. In vitro specific binding, cellular uptake, and internalization were determined. The tumor-targeting potential of [68Ga]Ga-DOTA-E(cRGDfK)2 in a lung cancer mouse model was studied. Besides, the very early diagnostic potential of the 68Ga-labeled RGD peptide was evaluated. The acquisition and reconstruction of the PET-CT image data were also carried out. Radiochemical and radionuclide purity for [68Ga]Ga-DOTA-E(cRGDfK)2 was >%98 and >%99, respectively. Radiotracer showed high in vivo, in vitro, and metabolic stability which was determined by ITLC. The dissociation constant (K d) of [68Ga]Ga-DOTA-E(cRGDfK)2 was 15.28 nM. On average, more than 95% of the radioactivity was specific binding (internalized + surface-bound) to A549 cells. Biodistribution data showed that radiolabeled peptides were accumulated significantly in A549 tumor and excreted rapidly by the renal system. Tumor uptake peaks were at 1-hour postinjection for [68Ga]Ga-DOTA-E(cRGDfK)2. The tumor was clearly visualized in all images. [68Ga]Ga-DOTA-E(cRGDfK)2 can be used as a peptide-based imaging agent allowing very early detection of different cancers overexpressing α v ß 3 integrin receptors and can be a potential candidate in clinical peptide-based imaging for lung cancer.

Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with α-glucosidase.

PURPOSE: One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postprandial hyperglycemia impaired the endogenous antioxidant defense due to inducing oxidative stress induced pancreatic ß-cell destruction through uncontrolled free radicals generation such as ROS, which in turn, leads to various macrovascular and microvascular complications. This study aimed to synthesize 2-aryl-4,6-diarylpyrimidine derivatives, screen their α-glucosidase inhibitory activity, perform kinetic and molecular docking studies. METHODS: A series of 3,4,5-triphenyl-4,5-dihydro-1,2,4-oxadiazole derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Compounds 6a-k were synthesized via a two-step reaction with a yield between 65 and 88%. The structural elucidation of the synthesized derivatives was performed by different spectroscopic techniques. α-Glucosidase inhibitory activity of the oxadiazole derivatives 6a-k was evaluated against Saccharomyces cerevisiae α-glucosidase. RESULTS: Most of the synthesized compounds demonstrated α-glucosidase inhibitory action. Particularly compounds 6c, 6d and 6 k were the most active compounds with IC50 values 215 ± 3, 256 ± 3, and 295 ± 4 µM respectively. A kinetic study performed for compound 6c revealed that the compound is a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 µM. The docking study also revealed that the two compounds, 6c and 6 k, have important binding interactions with the enzyme active site. CONCLUSION: The overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel α-glucosidase inhibitors to manage the postprandial hyperglycemia incidence. Graphical abstract.

Deep Eutectic Solvent Based Air Assisted Ligandless Emulsification Liquid-Liquid Microextraction for Preconcentration of Some Heavy Metals in Biological and Environmental Samples.

In this study, a deep eutectic solvent (DES) based on air-assisted ligandless emulsification liquid-liquid microextraction method (DES-AA-LL-ELLME) was considered for preconcentration and extraction of some metals (Cd, Ni, Pb and Cu). A 1:1 mixture of the synthesized DES and triethylamine was added as an extractant to extract metal ions in the absence of chelating agent. Tetrahydrofuran as the aprotic solvent provided a turbid state. To disperse the aggregated DES droplets into the aqueous phase, air-assisted was performed. The influence of several effective parameters was monitored. Under optimum conditions, limits of detection were found in the range of 0.31-0.99 µg L-1 with preconcentration factor from 67 to 69. The relative standard deviation (n = 10) was in the range of 2.1%-3.1% for all analytes. This procedure was applied to determine some metals in both biological and environmental samples with appropriate recoveries about 98.7%-106%.

Novel and Efficient Method for Solid Phase Synthesis of Urea-Containing Peptides Targeting Prostate Specific Membrane Antigen (PSMA) in Comparison with Current Methods.

The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully was applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys (OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.

Development of a 99mTc-Labeled CXCR4 Antagonist Derivative as a New Tumor Radiotracer.

Due to high expression of CXCR4 (CXC chemokine receptor type 4) receptors in many tumors and metastasis, synthesis and labeling of CXCR4 receptor-targeted analogs as tumor imaging agents have been encouraged. Herein, CXCR4 receptor-targeted peptide antagonist was prepared and thereafter its labeling with 99mTc by a bifunctional chelating agent and tricine coligand was developed. Radiotracer purity, stability, and tumor cell binding were assessed. Bioevaluation of radiotracer was performed in mice bearing xenograft tumor. More than 95% labeling yield and stability up to 24 hours were observed. Radiotracer-related tumor accumulation was 3.61 ± 0.15% ID/g at 1 hour postinjection. High stability and specific tumor uptake are important characteristics of the radiotracer that could nominate this as a targeted imaging agent in the future.

Correlation Between Polyphenol Oxidase (PPO) Activity and Total Phenolic Contents in Crocus sativus L. Corms During Dormancy and Sprouting Stages.

Purification and characterization of polyphenol oxidase (PPO) enzyme and determination of total phenolic contents during dormancy and sprouting stages in Crocus sativus corms were performed. PPO enzyme was purified by ammonium sulfate precipitation and ion-exchange chromatography using DEAE-Sephadex A25 and two isoenzymes were obtained on the SDS-PAGE, which corresponded to molecular weights of 70 and 54 kDa. The Km values of the enzyme were 4.87 and 2.12 mM for l-DOPA in dormancy and waking stages, respectively. Also, enzyme showed higher Vmax values of 0.026 (ΔOD.min-1) in dormancy compared with the value of 0.019 (ΔOD.min-1) in waking corms. Results showed an inverse correlation between phenolic contents and PPO activity. Accordingly, it can be concluded that as plant progressed through sprouting stage, in contrast to polyphenol oxidase activity, there was a significant increase in total amount of phenolic compounds, as determined by Folin-Ciocalteu method and water and aqueous ethanol extractions. SUMMARY: Purification of polyphenol oxidase enzyme using DEAE-Sephadex A25 in Crocus sativus corms.Characterization of polyphenol oxidase enzyme.Comparison of PPO enzyme characteristics in two different physiologic stages of dormancy and sprouting.Determination of phenolic contents.Correlation between phenolic contents and PPO activity during sprouting and dormancy. Abbreviations used: PPO: Polyphenol Oxidase, DEAE-Sephadex: Diethylaminoethyl Sephadex, SDS-PAGE: Sodium Dodecyl Sulfate- Polyacrylamide Gel Electrophoresis, DOPA: Dihydroxyphenylalanine, PEG: Polyethylene Glycol.

Dispersion of magnetic graphene oxide nanoparticles coated with a deep eutectic solvent using ultrasound assistance for preconcentration of methadone in biological and water samples followed by GC-FID and GC-MS.

Magnetic graphene nanoparticles coated with a new deep eutectic solvent (Fe3O4@GO-DES) were developed for efficient preconcentration of methadone. The extracted methadone was then analyzed by gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS). Fe3O4@GO-DES were characterized by Fourier transform IR and X-ray diffraction techniques. Ultrasound was used to enhance the dispersion of the sorbent, with a high extraction recovery. Some parameters affecting the extraction recovery, such as pH, type of deep eutectic solvent, sample volume, amount of sorbent, extraction time, and type of eluent, were investigated. Under optimum conditions, the method developed was linear in the concentration range from 3 to 45,000 µg L-1 for GC-FID and from 0.1 to 500 µg L-1 for GC-MS, with a detection limit of 0.8 µg L-1 for GC-FID and 0.03 µg L-1 for GC-MS. The relative standard deviations (n = 6) as the intraday and interday precisions of the methadone spike at a concentration of 100 µg L-1 were 5.8% and 8.4% respectively for GC-FID. The preconcentration factor was 250. Relative recoveries from spiked plasma, urine, and water samples ranged from 95.1% to 101.5%.

Ion-pair switchable-hydrophilicity solvent-based homogeneous liquid-liquid microextraction for the determination of paraquat in environmental and biological samples before high-performance liquid chromatography.

An approach involving ion-pair switchable-hydrophilicity solvent-based homogeneous liquid-liquid microextraction coupled to high-performance liquid chromatography has been applied for the preconcentration and separation of paraquat in a real sample. A mixture of triethylamine and water was used as the switchable-hydrophilicity solvent. The pH was regulated using carbon dioxide; hence the ratio of the ionized and non-ionized form of triethylamine could control the optimum conditions. Sodium dodecyl sulfate was utilized as an ion-pairing agent. The ion-associate complex formed between the cationic paraquat and sodium dodecyl sulfate was extracted into triethylamine. The separation of the two phases was carried out by the addition of sodium hydroxide, which changed the ionization state of triethylamine. The effects of some important parameters on the extraction recovery were investigated. Under the optimum conditions (500 µL of the extraction solvent, 1 mg sodium dodecyl sulfate, 2.0 mL of 10 mol/L sodium hydroxide, and pH 4), the limit of detection and the limit of quantification were 0.2 and 0.5 µg/L, respectively, with preconcentration factor of 74. The precision (RSD, n = 10) was  <5%. The recovery of the analyte in environmental and biological samples was in the range of 90.0-92.3%.