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1.
J Nucl Med ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054284

RESUMEN

Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. 64CuCl2 , a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of 64CuCl2-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and 18F-FDG PET/CT. Methods: We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, 18F-FDG, and 64CuCl2 PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). Results: Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and 64CuCl2 PET/CT showed higher sensitivity than 18F-FDG PET/CT in detecting the primary tumor (P < 0.001); moreover, 64CuCl2 PET/CT was slightly more sensitive than 18F-FDG PET/CT in disclosing soft-tissue lesions (P < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (P < 0.05). On lesion-based analysis, 64CuCl2 PET/CT outperformed 18F-FDG PET/CT and ceCT in detecting disease localizations overall (P < 0.001), in the lymph nodes (P < 0.01), in the skeleton (P < 0.001), and in the soft tissue (P < 0.05). Conclusion: 64CuCl2 PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a "one-stop shop" diagnostic method in these scenarios.

2.
Mol Divers ; 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38267750

RESUMEN

Research on the synthesis of imidazo[1,2-a]pyridines has gained great importance among synthetic chemists because there have been numerous reports of their biological and medicinal activities. In this respect, we fabricated CuCl2 immobilized on Fe3O4 nanoparticles modified with 1,10-phenanthroline-5,6-diol [Fe3O4@Diol/Phen-CuCl2] and investigated its catalytic activity for the preparation of imidazo[1,2-a]pyridine derivatives through one-pot three-component reaction of 2-aminopyridines, aldehydes and terminal alkynes under ecofriendly conditions. FT-IR spectroscopy, EDX, SEM, TEM, XRD, TGA, VSM and ICP-OES techniques employed in order to identify the structure of the as-constructed Fe3O4@Diol/Phen-CuCl2 nanocatalyst. This catalytic system has a series of advantages such as the synthesis of imidazo[1,2-a]pyridine products with high yields in suitable time, performing the reactions in an environmentally friendly solvent (PEG), easy preparation of the catalyst with a simple method, and the recyclability of the Fe3O4@Diol/Phen-CuCl2 nanocatalyst.

3.
J Environ Health Sci Eng ; 21(1): 73-83, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37159741

RESUMEN

The final and most crucial step in obtaining clean water is disinfection. More innovative methods of water disinfection have recently been sought. Water disinfection is a promising application for nanoparticles as disinfectants. As a contribution to the literature, biofilm and metal-containing nanoparticles as antiadhesion inhibitors were used in conjunction with ultrasound in this study. The microbroth dilution test was used to reveal the microbiological antibacterial activities of different concentrations of AgNO3 and CuCl2 containing nanoparticles against the Escherichia coli ATCC 25,922 strain, which is an indicator bacterium in water systems. Antibiofilm activities were then investigated using biofilm attachment and biofilm inhibition tests. The inhibitory effect of nanoparticle ultrasonic waves on biofilm contamination was determined using a novel approach. Human keratinocyte cells (HaCaT cell line) were used in cell culture studies after water disinfection, and their cytotoxic effects were demonstrated using the MTT assay. The findings suggest that the nanoparticles utilized might be a viable choice for water disinfection applications. Furthermore, employing ultrasound at low doses with nanoparticles resulted in greater results. One feasible option is to employ nanoparticles to cleanse water without producing cytotoxicity.

4.
J Mol Model ; 29(5): 136, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37045992

RESUMEN

CONTEXT: At present, sulfonamides and their metal complexes have received a new impetus for development. Of particular interest is the study of molecular and crystal structures, which takes into account weak non-valent interactions. Despite the low energy of such interactions, in many cases, they act collectively, and the sum of their actions can play a significant role. As a result, the spectrum of medical and biological activity of new metal complexes is expanded. In this regard, the synthesis and study of the molecular and crystal structure of sulfonamides and their metal complexes is of undoubted relevance. In this work, we studied non-valent intra- and intermolecular interactions in ligands of sulfonamide-substituted imidazo[2,1-b]thiazoles and their previously unknown complexes with CuCl2. The performed analysis of the data obtained by X-ray diffraction analysis made it possible to establish the intramolecular π-stacking interaction in imidazothiazole ligands, which is retained in their complexes with CuCl2. Within the framework of QTAIM topological analysis of electron density and DORI analysis, stereoelectronic and topological structures were studied. In the complexes, tetral, chalcogen, and pnycogen new interligand non-valent interactions were established. The energies of all established types of non-valent interactions have been calculated, and their comparative evaluation has been made. METHODS: X-ray data of new arylsulfonylamino-substituted derivatives of imidazo[2,1-b]thiazoles and their metal complexes with CuCl2 have been studied. To determine the theoretical prerequisites for the occurrence of π-stacking in the molecules under study, the QTAIM method was used in the framework of the DFT/B3LYP/6-311 + G(d) calculation using the GAUSSIAN 09 program. In addition, the DORI electron density region overlap indicator and the Multiwfn program were used to analyze non-valent interactions.

5.
Nanotechnology ; 34(30)2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37094553

RESUMEN

SnO2film is one of the most widely used electron transport layers (ETL) in perovskite solar cells (PSCs). However, the inherent surface defect states in SnO2film and mismatch of the energy level alignment with perovskite limit the photovoltaic performance of PSCs. It is of great interesting to modify SnO2ETL with additive, aiming to decrease the surface defect states and obtain well aligned energy level with perovskite. In this paper, anhydrous copper chloride (CuCl2) was employed to modify the SnO2ETL. It is found that the adding of a small amount of CuCl2into the SnO2ETL can improve the proportion of Sn4+in SnO2, passivate oxygen vacancies at the surface of SnO2nanocrystals, improve the hydrophobicity and conductivity of ETL, and obtain a good energy level alignment with perovskite. As a result, both the photoelectric conversion efficiency (PCE) and stability of the PSCs based on SnO2ETLs modified with CuCl2(SnO2-CuCl2) is improved in comparison with that of the PSCs on pristine SnO2ETLs. The optimal PSC based on SnO2-CuCl2ETL exhibits a much higher PCE of 20.31% as compared to the control device (18.15%). The unencapsulated PSCs with CuCl2modification maintain 89.3% of their initial PCE after exposing for 16 d under ambient conditions with a relative humidity of 35%. Cu(NO3)2was also employed to modify the SnO2ETL and achieved a similar effect as that of CuCl2, indicating that the cation Cu2+plays the main role in SnO2ETL modification.

6.
J Nanobiotechnology ; 21(1): 86, 2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36906540

RESUMEN

Programmed cell death ligand 1 protein-positive (PD-L1+) exosomes have been found to be a potential biomarker for the diagnosis of non-small cell lung cancer (NSCLC). However, the development of highly sensitive detection technique for PD-L1+ exosomes is still a challenge in clinical applications. Herein, a sandwich electrochemical aptasensor based on ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres (PdCuB MNs) and Au@CuCl2 nanowires (NWs) was designed for the detection of PD-L1+ exosomes. The excellent peroxidase-like catalytic activity of PdCuB MNs and the high conductivity of Au@CuCl2 NWs endow the fabricated aptasensor with intense electrochemical signal, thus enabling the detection of low abundance exosomes. The analytical results revealed that the aptasensor maintained favorable linearity over a wide concentration range of 6 orders of magnitude and reached a low detection limit of 36 particles/mL. The aptasensor is successfully applied to the analysis of complex serum samples and achieves the accurate identification of clinical NSCLC patients. Overall, the developed electrochemical aptasensor provides a powerful tool for early diagnosis of NSCLC.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Nanopartículas del Metal , Nanocables , Humanos , Antígeno B7-H1 , Técnicas Biosensibles/métodos , Límite de Detección , Oro
7.
Chem Asian J ; 18(1): e202200954, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36378015

RESUMEN

Here we report a copper-catalyzed protocol for the synthesis of α-chloroketones from aromatic alkenes including electron-deficient olefins under visible-light irradiation. Preliminary mechanistic studies show that the peroxo Cu(II) species is the key intermediate and hydroperoxyl (HOO⋅) and chlorine (Cl⋅) radicals can be generated by ligand-to-metal charge transfer (LMCT).


Asunto(s)
Alquenos , Luz , Cobre , Catálisis
8.
Biol Trace Elem Res ; 201(7): 3367-3380, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36068418

RESUMEN

Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl2), a Cu(II) compound, on various parameters of oxidative stress, cellular metabolism, and DNA integrity in the rat kidney. This was done to delineate the molecular mechanism of Cu(II) toxicity. Adult male rats were randomly divided into five groups. Animals in four CuCl2-treated groups were separately administered single acute oral dose of CuCl2 at 5, 15, 30, and 40 mg/kg body weight. Animals in the fifth group were not given CuCl2 and served as the control. All rats were sacrificed 24 h after the dose of CuCl2 and their kidneys removed. CuCl2 administration led to significant alterations in enzymatic and non-enzymatic parameters of oxidative stress. It changed the activities of metabolic and membrane bound enzymes and also decreased the activities of brush border membrane enzymes. CuCl2 treatment dose-dependently enhanced DNA damage and DNA-protein crosslinking in renal cells, when compared to the control group. The administration of CuCl2 also resulted in marked morphological changes in the kidney, with more prominent alterations at higher doses of CuCl2. These results clearly show that CuCl2 impairs the antioxidant defense system resulting in oxidative damage to the kidney.


Asunto(s)
Antioxidantes , Cobre , Humanos , Masculino , Ratas , Animales , Antioxidantes/metabolismo , Cobre/metabolismo , Cloruros/farmacología , Estrés Oxidativo , Riñón/metabolismo , Administración Oral , Daño del ADN
9.
Mol Imaging Biol ; 25(2): 391-400, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36042116

RESUMEN

PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.


Asunto(s)
Glioma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Femenino , Humanos , Niño , Adolescente , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Cobre , Glioma/patología , Radioisótopos de Cobre , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones/métodos
10.
Cell Biol Toxicol ; 39(5): 2311-2329, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-35877023

RESUMEN

In dose-response and structure-activity studies, human hepatic HepG2 cells were exposed for 3 days to nano Cu, nano CuO or CuCl2 (ions) at doses between 0.1 and 30 ug/ml (approximately the no observable adverse effect level to a high degree of cytotoxicity). Various biochemical parameters were then evaluated to study cytotoxicity, cell growth, hepatic function, and oxidative stress. With nano Cu and nano CuO, few indications of cytotoxicity were observed between 0.1 and 3 ug/ml. In respect to dose, lactate dehydrogenase and aspartate transaminase were the most sensitive cytotoxicity parameters. The next most responsive parameters were alanine aminotransferase, glutathione reductase, glucose 6-phosphate dehydrogenase, and protein concentration. The medium responsive parameters were superoxide dismutase, gamma glutamyltranspeptidase, total bilirubin, and microalbumin. The parameters glutathione peroxidase, glutathione reductase, and protein were all altered by nano Cu and nano CuO but not by CuCl2 exposures. Our chief observations were (1) significant decreases in glucose 6-phosphate dehydrogenase and glutathione reductase was observed at doses below the doses that show high cytotoxicity, (2) even high cytotoxicity did not induce large changes in some study parameters (e.g., alkaline phosphatase, catalase, microalbumin, total bilirubin, thioredoxin reductase, and triglycerides), (3) even though many significant biochemical effects happen only at doses showing varying degrees of cytotoxicity, it was not clear that cytotoxicity alone caused all of the observed significant biochemical effects, and (4) the decreased glucose 6-phosphate dehydrogenase and glutathione reductase support the view that oxidative stress is a main toxicity pathway of CuCl2 and Cu-containing nanomaterials.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanoestructuras , Humanos , Cobre/toxicidad , Células Hep G2 , Glutatión Reductasa/metabolismo , Glutatión Reductasa/farmacología , Estrés Oxidativo , Nanoestructuras/toxicidad , Bilirrubina/metabolismo , Bilirrubina/farmacología , Fosfatos/farmacología , Glucosa
11.
Molecules ; 27(21)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36364217

RESUMEN

The efficient "One-pot" CuCl2-catalyzed C-S bond coupling reactions were developed for the synthesis of dibenzo[b,f][1,4]thiazepines and 11-methy-ldibenzo[b,f][1,4]thiazepines via 2-iodobenzaldehydes/2-iodoacetophenones with 2-aminobenzenethiols/2,2'-disulfanediyldianilines by using bifunctional-reagent N, N'-dimethylethane-1,2-diamine (DMEDA), which worked as ligand and reductant. The reactions were compatible with a range of substrates to give the corresponding products in moderate to excellent yields.


Asunto(s)
Diaminas , Tiazepinas , Catálisis , Indicadores y Reactivos , Dibenzotiazepinas
12.
Polymers (Basel) ; 14(20)2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36297966

RESUMEN

The growing issue of particulate matter (PM) air pollution has given rise to extensive research into the development of high-performance air filters recently. As the core of air filters, various types of electrospun nanofiber membranes have been fabricated and developed. With the novel poly(acrylonitrile) (PAN)-CuCl2 composite nanofiber membranes as the filter membranes, we demonstrate the high PM removal efficiency exceeding 99% and can last a long service time. The nanoscale morphological characteristics of nanofiber membranes were investigated by scanning electron microscopy, transmission electron microscopy, and mercury intrusion porosimeter. It is found that they appear to have a special net structure at specific CuCl2 concentrations, which substantially improves PM removal efficiency. We anticipate the PAN-CuCl2 composite nanofiber membranes will be expected to effectively solve some pressing problems in air filtration.

13.
Molecules ; 27(15)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35956819

RESUMEN

64CuCl2 is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of 64CuCl2 in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. 18F-FDG was used as a comparator. Twenty-two animals were imaged 7-9 days following 4T1-cell implantation inside mammary glands. Dynamic 64CuCl2 µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning 18F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor 64CuCl2 accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle 64CuCl2 accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The 18F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. 64CuCl2 PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.


Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias de la Mama Triple Negativas , Aloinjertos , Animales , Línea Celular Tumoral , Humanos , Ratones , Ratones Endogámicos BALB C , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones/métodos , Distribución Tisular , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen
14.
ChemSusChem ; 15(17): e202200957, 2022 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-35730105

RESUMEN

A visible light-induced oxidative α-keto-dichlorination of terminal and internal aryl alkynes was developed to form dichloroacetophenones (DCAPs) and dichlorophenyl-acetophenones (DCPAPs), respectively, by using CuCl2 as a photoredox catalyst in the presence of air at room temperature (without using any exogenous photocatalyst). Here, photoexcited CuCl2 underwent ligand-to-metal charge transfer to generate a Cl radical, which readily added to the alkynes to form DCAPs or DCPAPs in the presence of O2 . This α-keto-dichlorination reaction is a green and mild protocol as it produced water as the only by-product. Moreover, the evaluation of green chemistry metrics indicated that the E-factor (mass of wastes/mass of products) of the current α-keto-chlorination method is around 10.1 times lower than that of a literature-reported photochemical method. The Eco Scale value (score 55, which on a scale of 0-100 indicates an acceptable synthesis) signifies that this process is simple, highly efficient, eco-friendly, and cost-effective.


Asunto(s)
Alquinos , Luz , Oxidación-Reducción , Estrés Oxidativo , Temperatura
15.
Artículo en Inglés | MEDLINE | ID: mdl-35652577

RESUMEN

Hydrogen sulfide (H2S) sensors are in urgent demand in the field of hermetic environment detection and metabolic disease diagnosis. However, most of the reported room-temperature (RT) H2S sensors based on transition metal oxides/salts unavoidably suffer from the poisoning effect, resulting in the unrecoverable behavior to restrain their application. Herein, copper(II) chloride-doped polyaniline emeraldine salt (PANI-CuCl2) was devised for RT-recoverable H2S detection, where the copper ion (Cu2+) was designed as a partial substitution of protons (H+) in PANI. The prepared gas sensor exhibited full recovery capability toward 0.25-10 ppm H2S, good repeatability, and long-term stability under 80% RH. Meanwhile, the changes of the PANI-CuCl2 during the H2S sensing period were analyzed via multiple analytical methods to reveal the reversible sensing behavior. Results showed that doping of Cu2+ not only promoted the PANI's response through the formation of conductive copper sulfide (CuS) and following H+ redoping in the PANI but also facilitated the sensor's recovery behavior because of the Cu2+ regeneration under the H+/oxygen environment. This work not only proves the changes of the interaction between the PANI and Cu2+ during the H2S sensing period but also sheds light on designing recoverable H2S sensors based on transition metal salts.

16.
Prostate ; 82(7): 858-866, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35286730

RESUMEN

BACKGROUND: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC used DSF as monotherapy. OBJECTIVE: To assess the safety and efficacy of concurrent administration of DSF with Cu, we conducted a phase 1b clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Cu with DSF. DESIGN, SETTING, AND PARTICIPANTS: Patients with mCRPC were treated in two cohorts: mCRPC with nonliver/peritoneal metastases (A), and mCRPC with liver and/or peritoneal metastases (B). Baseline Cu avidity was measured by 64 CuCl2 PET scan. Intravenous (IV) CuCl2 was given weekly for three doses with oral daily DSF followed by daily oral Cu gluconate and DSF until disease progression. DSF and metabolite diethyldithiocarbamic acid methyl ester (Me-DDC) levels in plasma were measured. DSF and Me-DDC were then assessed for cytotoxicity in vitro. RESULTS: We treated nine patients with mCRPC (six on cohort A and three on cohort B). Bone and nodal metastases showed differential and heterogeneous Cu uptake on 64 CuCl2 PET scans. No confirmed PSA declines or radiographic responses were observed. Median PFS was 2.8 months and median OS was 8.3 months. Common adverse events included fatigue and psychomotor depression; no Grade 4/5 AEs were observed. Me-DDC was measurable in all samples (LOQ = 0.512 ng/ml), whereas DSF was not (LOQ = 0.032 ng/ml, LOD = 0.01 ng/ml); Me-DDC was not cytotoxic in vitro. CONCLUSIONS: Oral DSF is not an effective treatment for mCRPC due to rapid metabolism into an inactive metabolite, Me-DDC. This trial has stopped enrollment and further work is needed to identify a stable DSF formulation for treatment of mCRPC.


Asunto(s)
Neoplasias Peritoneales , Neoplasias de la Próstata Resistentes a la Castración , Cobre/uso terapéutico , Disulfiram/uso terapéutico , Humanos , Masculino , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico
17.
Med Phys ; 49(4): 2709-2724, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35134261

RESUMEN

PURPOSE: 64 Cu and 67 Cu radioisotopes have nuclear characteristics suitable for nuclear medicine applications. The production of 64 Cu is already well established. However, the production of 67 Cu in quantities suitable to conduct clinical trials is more challenging as it leads to the coproduction of other Cu isotopes, in particular 64 Cu. The aim of this study is to investigate the possibility of using a CuCl2 solution with a mixture of 67/64 Cu radioisotopes for therapeutic purposes, providing an alternative solution for the cyclotron production problem. METHODS: Copper radioisotopes activities were calculated by considering proton beam irradiation of the following targets: (i) 70 Zn in the energy range 70-45 MeV; (ii) 68 Zn in the energy range 70-35 MeV; (iii) a combination of 70 Zn (70-55 MeV) and 68 Zn (55-35 MeV). The contribution of each copper radioisotope to the human-absorbed dose was estimated with OLINDA/EXM software using the biokinetic model for CuCl2 published by ICRP 53. The total absorbed dose generated by the 67/64 CuCl2 mixture, obtained through different production routes, was calculated at different times after the end of the bombardment (EOB). A simple spherical model was used to simulate tumors of different sizes containing uniformly distributed 67/64 Cu mixture and to calculate the absorbed dose of self-irradiation. The biological damage produced by 67 Cu and 64 Cu was also evaluated through cellular dosimetry and cell surviving fraction assessment using the MIRDcell code, considering two prostate cancer cell lines with different radiosensitivity. RESULTS: The absorbed dose to healthy organs and the effective dose (ED) per unit of administered activity of 67 CuCl2 are higher than those of 64 CuCl2 . Absorbed dose values per unit of administered activity of 67/64 CuCl2 mixture increase with time after the EOB because the amount of 67 Cu in the mixture increases. Survival data showed that the biological damage caused per each decay of 67 Cu is greater than that of 64 Cu, assuming that radionuclides remain accumulated in the cell cytoplasm. Sphere model calculations demonstrated that 64 Cu administered activity must be about five times higher than that of 67 Cu to obtain the same absorbed dose for tumor mass between 0.01 and 10 g and about 10 times higher for very small spheres. Consequently, the 64 CuCl2 -absorbed dose to healthy organs will reach higher values than those of 67 CuCl2 . The supplemental activity of the 67/64 CuCl2 mixture, required to get the same tumor-absorbed dose produced by 67 CuCl2 , triggers a dose increment (DI) in healthy organs. The waiting time post-EOB necessary to keep this DI below 10% (t10% ) depends on the irradiation methods employed for the production of the 67/64 CuCl2 mixture. CONCLUSIONS: A mixture of cyclotron produced 67/64 Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl2 with minimal DI to healthy organs compared with pure 67 Cu. Irradiation of a 70 Zn+68 Zn target in the 70-35 MeV proton energy range for 185 h appears to be the best option from among all the production routes investigated, as it gives the maximum amount of activity, the shortest t10% (10 h), and less than 1% of 61 Cu and 60 Cu impurities.


Asunto(s)
Ciclotrones , Neoplasias , Radioisótopos de Cobre , Estudios de Factibilidad , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Protones , Radioisótopos/uso terapéutico , Radiofármacos
18.
J Clin Med ; 12(1)2022 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-36615024

RESUMEN

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (64Cu), a form of copper chloride (64CuCl2), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (68Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of 64CuCl2 that make it an ideal theragnostic nuclide. Indeed, 64CuCl2 emits ß+ and ß- particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of 64CuCl2 for the radionuclide cancer therapy of copper-avid tumors. Recently, 64CuCl2 was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, 64CuCl2 PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.

19.
ACS Appl Mater Interfaces ; 13(37): 44274-44283, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34503328

RESUMEN

A water-stable thin film composed of C6H4NH2CuCl2I was fabricated using spin-coating precursor solutions that dissolved equimolar amounts of C6H4NH2I and CuCl2 in N,N-dimethylformamide. Photoelectrochemical characteristics show that the C6H4NH2CuCl2I film demonstrated a stable photocurrent (∼1 µA/cm2) in an aqueous solution under white light (11.5 mW/cm2) even after 3000 s, while exhibiting a photon-to-current efficiency of 0.093% under AM1.5 (100 mW/cm2) illumination. However, these values were significantly lower than those of the CH3NH3PbX3 (X = I, Cl) film in solid devices. The electron diffusion length L(e-) (373 nm) and hole diffusion length L(h+) (177 nm) in the C6H4NH2CuCl2I photoelectrode were significantly lower than those of CH3NH3PbX3, limiting the photoelectrochemical and photocatalysis performances. Moreover, L(h+) was shorter than L(e-) in the C6H4NH2CuCl2I photoelectrode, resulting in the hole-collecting efficiency [ηc(h+)] being lower than the electron-collecting efficiency [ηc(e-)]. A CuO interlayer was introduced as a hole transport layer for the C6H4NH2CuCl2I photoelectrode, which improved L(h+) and ηc(h+).

20.
J Trace Elem Med Biol ; 68: 126844, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34425455

RESUMEN

BACKGROUND: Phoxim is a widely used organophosphorus pesticide in agriculture. People are paying more and more attention to its toxicity. At present, there is no appropriate way to solve the phoxim poisoning of silkworm, which severely affected the development of sericulture. Fe2+, Cu2+, Rb+ exerted their biological effects through various forms in vivo. METHODS: To evaluate the effect of Fe2+/Cu2+/Rb+ on phoxim poisoning in silkworm, Bombyx mori were treated with fresh mulberry leaves soaked in 2.5 mg/L phoxim for 2 min with 50 mg/L FeCl2, 150 mg/L CuCl2, or 0.5 mg/L RbCl from 5 days of the fifth-instar silkworm. RESULTS: Fe2+, Cu2+, and Rb+ pretreatments significantly inhibited the phoxim-induced reduction of survival rate and alleviated the phoxim-induced poisoning symptoms. The protective effects of Fe2+, Cu2+, and Rb+ on phoxim poisoning might be due to their enhancement of superoxide dismutase (SOD), catalase (CAT), and carboxylesterase (CarE) in the hemolymph and fat body of silkworm. This enhancement might reduce reactive oxygen species (ROS) accumulation and oxidative stress (OS) caused by phoxim poisoning. Thereby it reduced the damage to silkworm tissues and cells. CONCLUSIONS: These results showed that Fe2+, Cu2+, and Rb+ treatments protected the silkworm from phoxim poisoning by directly enhancing the activity of SOD, CAT, and CarE enzymes and reducing oxidative stress, but not dependent on the high expression of CYP genes. The use of Fe2+, Cu2+, and Rb+ to enhance the activity of SOD, CAT, and CarE enzymes may be an underlying effective way to solve phoxim poisoning in the silkworm industry.


Asunto(s)
Bombyx , Insecticidas , Compuestos Organotiofosforados/toxicidad , Animales , Insecticidas/toxicidad , Compuestos Organofosforados , Plaguicidas , Superóxido Dismutasa
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