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1.
Chemistry ; 27(2): 669-682, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-32700787

RESUMEN

Carbon-based symmetric supercapacitors (SCs) are known for their high power density and long cyclability, making them an ideal candidate for power sources in new-generation electronic devices. To boost their electrochemical performances, deriving activated carbon doped with heteroatoms such as N, O, and S are highly desirable for increasing the specific capacitance. In this regard, activated carbon (AC) self-doped with heteroatoms is directly derived from bio-waste (lima-bean shell) using different KOH activation processes. The heteroatom-enriched AC synthesized using a pretreated carbon-to-KOH ratio of 1:2 (ONS@AC-2) shows excellent surface morphology with a large surface area of 1508 m2 g-1 . As an SC electrode material, the presence of heteroatoms (N and S) reduces the interfacial charge-transfer resistance and increases the ion-accessible surface area, which inherently provides additional pseudocapacitance. The ONS@AC-2 electrode attains a maximum specific capacitance (Csp ) of 342 F g-1 at a specific current of 1 Ag-1 in 1 m NaClO4 electrolyte at the wide potential window of 1.8 V. Moreover, as symmetric SCs the ONS@AC-2 electrode delivers a maximum specific capacitance (Csc ) of 191 F g-1 with a maximum specific energy of 21.48 Wh kg-1 and high specific power of 14 000 W kg-1 and excellent retention of its initial capacitance (98 %) even after 10000 charge/discharge cycles. In addition, a flexible supercapacitor fabricated utilizing ONS@AC-2 electrodes and a LiCl/polyvinyl alcohol (PVA)-based polymer electrolyte shows a maximum Csc of 119 F g-1 with considerable specific energy and power.

2.
Environ Monit Assess ; 191(12): 720, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31691038

RESUMEN

We evaluated the efficiency of an air purifier using the single-chamber method for the effective removal of airborne Staphylococcus epidermidis, a nosocomial infection-causing bacterium. In this experiment, the bacterial strain S. epidermidis was injected using a nebulizer into the test chamber, which was similar to a consumer living space (60 m3). The microbial sampling was conducted via the air sampler method, and the reduction in S. epidermidis growth was monitored by performing three consecutive tests. Initially, a blank test was conducted to determine the natural decay rate and calibrate the experimental setup. After injecting the bacterial strain from 1240 to 11180 CFU per unit volume (m3), the natural decay rate showed a maximum deviation of 3.1% with a sampling error of 1.1% p at a confidence level of 95%. In addition, the particle size distribution in the test chamber was found to range from 0.3 to 5.0 µm, and a subsequent decrease in large-sized particles was observed with the operation of the air purifier, which is the size similar to that of suspended airborne bacteria. This can be used to assess the performance of the air purifier by calibrating the natural reduction value to the reduced operation value. Thus, the single-chamber technique is a promising approach for analyzing the removal efficacy of airborne bacteria from indoor air.


Asunto(s)
Filtros de Aire/normas , Microbiología del Aire , Staphylococcus epidermidis/aislamiento & purificación , Monitoreo del Ambiente , Tamaño de la Partícula
3.
J Labelled Comp Radiopharm ; 56(14): 731-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24339013

RESUMEN

Bases such as potassium carbonate and potassium bicarbonate (KHCO3 ) are essential for the elution of trapped [(18) F]fluoride from ion exchange cartridges and for the prevention of [(18) F]fluoride adsorption on the silica glass vial during the preparation of radiopharmaceuticals for positron emission tomography imaging. However, these bases promote the chemical decomposition of precursor compounds and the creation of unwanted organic impurities. Thus, the goal of the current study was to develop a new method for synthesizing [(18) F]fluoride-labeled radiopharmaceuticals (e.g., [(18) F]fluoromisonizadole ([(18) F]FMISO)) that permits the fine control of base concentrations while minimizing adverse events. Non-decay-corrected radiochemical yields of 25.1 ± 5.0% and 13.3 ± 5.1% (n = 3) were achieved after solid-phase extraction purification using automatic synthesis with GE TRACERlab MX and KHCO3 at concentrations of 14.1 and 33.0 µmol, respectively, and 1 mg of precursor (1-(2'-nitro-1'-imidazolyl)-2-O-tetra-hydropyranyl-3-O-toluenesulfonyl propanediol (NITTP)). The newly developed synthesis protocol with fine base control and low precursor content permits high radiochemical yields with minimal impurities.


Asunto(s)
Marcaje Isotópico/métodos , Misonidazol/análogos & derivados , Radiofármacos/síntesis química , Misonidazol/síntesis química , Misonidazol/aislamiento & purificación , Radiofármacos/aislamiento & purificación , Extracción en Fase Sólida
4.
Bioconjug Chem ; 23(3): 431-7, 2012 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-22264022

RESUMEN

Lipophilic cations such as phosphonium salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria in response to the negative inner-transmembrane potentials. Thus, as newly developed noninvasive imaging agents, [(18)F]-labeled phosphonium salts may serve as molecular "voltage sensor" probes to investigate the role of mitochondria, particularly in myocardial disease. The present study reports the radiosynthesis of (6-fluorohexyl)triphenylphosphonium salt (3) as a potential agent for myocardial imaging by using positron emission tomography (PET). The reference compound of (6-[(18)F]fluorohexyl)triphenylphosphonium salt ([(18)F]3) was synthesized with 74% yield via three-step nucleophilic substitution reactions. The reference compound was radiolabeled via two-step nucleophilic substitution reactions of no-carrier-added [(18)F]fluoride with the precursor hexane-1,6-diyl bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K(2)CO(3). The radiolabeled compound was synthesized with 15-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >6.10-6.47 TBq/µmol. The cellular uptake assay showed preferential uptake of [(18)F]3 in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]3 in mice and rats showed preferential accumulation in the myocardium. The results suggest that this compound would be a promising candidate for myocardial imaging.


Asunto(s)
Radioisótopos de Flúor , Corazón/anatomía & histología , Fosfinas , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Animales , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa Bombardeada por Átomos Veloces
5.
Bioorg Med Chem Lett ; 22(1): 319-22, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-22133630

RESUMEN

[(18)F]-labeled molecular probe for the detection of myocardial perfusion deficit is driving particular interest due to its high clinical applicability. Thus, we synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)triphenylphosphonium salt ([(18)F]3) that specifically accumulates in myocardium according to mitochondrial membrane potential. Here, we evaluated the performance of [(18)F]3 as a mitochondrial voltage sensor in vitro and in vivo. The [(18)F]3 was synthesized with 20∼30% radiochemical yield and radiochemical purity was >98% by analytical HPLC. Specific activity was >6.7TBq/µmol. The cellular uptake assay showed preferential uptake of [(18)F]3 in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]3 in mice and rats showed preferential accumulation in the myocardium. The results suggest that this compound would be a promising candidate for myocardial imaging.


Asunto(s)
Miocardio/patología , Compuestos Organofosforados/química , Tomografía de Emisión de Positrones/métodos , Animales , Cationes , Cromatografía Líquida de Alta Presión/métodos , Diseño de Fármacos , Radioisótopos de Flúor/farmacología , Iones , Espectroscopía de Resonancia Magnética/métodos , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Modelos Químicos , Miocitos Cardíacos/citología , Perfusión , Ratas , Factores de Tiempo , Distribución Tisular
6.
Bioorg Med Chem Lett ; 22(16): 5288-92, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22796183

RESUMEN

Malignant melanoma displays a highly aggressive metastasis. Thus, early diagnosis of malignant melanoma is important for patient survival. We designed and synthesized a novel (68)Ga-labeled benzamide derivative that specifically binds to melanoma as demonstrated by its ability to bind to melanin. (68)Ga-SCN-DOTA-PCA was synthesized with a radiochemical yield of ~80% and a radiochemical purity of >97% by analytical HPLC. The in vitro binding of (68)Ga-SCN-DOTA-PCA to melanin and its cellular uptake demonstrated the selective uptake in melanin. In addition, the biodistribution and micro-PET imaging of (68)Ga-SCN-DOTA-PCA in B16F10 tumor models showed the specific accumulation in melanoma. These results suggest that (68)Ga-SCN-DOTA-PCA would be a promising agent for melanoma diagnosis.


Asunto(s)
Benzamidas/química , Compuestos Heterocíclicos con 1 Anillo/química , Melanoma Experimental/diagnóstico por imagen , Radiofármacos/síntesis química , Animales , Benzamidas/síntesis química , Benzamidas/farmacocinética , Línea Celular Tumoral , Radioisótopos de Galio/química , Semivida , Ratones , Ratones Endogámicos C57BL , Tomografía de Emisión de Positrones , Procainamida/química , Radiofármacos/farmacocinética , Distribución Tisular , Trasplante Homólogo
7.
Bioorg Med Chem ; 20(16): 4915-20, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22831797

RESUMEN

Radiolabeled benzamides have been reported to be attractive agents for targeting malignant melanoma as they bind melanin and display high accumulation in melanoma cells. Herein, we report the synthesis and bioevaluation of a novel (68)Ga-labeled benzamide as a potential PET agent for malignant melanoma. The novel radiotracer was synthesized in good radiochemical yields (80% decay corrected yield) and high specific radioactivity (10 GBq/µmol). Cellular uptake of (68)Ga-SCN-NOTA-BZA was significantly higher in B16F10 cells (mouse melanoma) treated with L-tyrosine. Biodistribution and micro-PET studies of (68)Ga-SCN-NOTA-BZA in B16F10-bearing mice showed selective uptake into the tumor. The radiotracer was cleared via renal excretion without further metabolism. These results demonstrate that (68)Ga-SCN-NOTA-BZA is a potential PET probe for malignant melanoma.


Asunto(s)
Benzamidas , Melanoma Experimental/diagnóstico , Tomografía de Emisión de Positrones , Radiofármacos/síntesis química , Animales , Benzamidas/síntesis química , Benzamidas/química , Línea Celular Tumoral , Modelos Animales de Enfermedad , Radioisótopos de Galio , Ratones , Radiofármacos/farmacocinética
8.
J Nanosci Nanotechnol ; 11(2): 1818-21, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21456300

RESUMEN

In this study, we have successfully developed 3-[131I]iodo-tyrosine grafted Fe3O4@SiO2 nanocomposites for dual potential tumor imaging agent for SPECT and MRI. Fe3O4 nanoparticle was synthesized through thermal decomposition and Fe3O4@SiO2 was prepared by reverse microemulsion method. After conjugating aminopropyltriethoxysiliane, L-tyrosine was introduced by amide coupling reaction. Finally, [131I]iodide was labeled on L-tyrosine grafted Fe3O4@SiO2 nanocomposite by aromatic iodination using chloramine-T.


Asunto(s)
Monoyodotirosina/química , Nanocompuestos/química , Dióxido de Silicio/química , Radioisótopos de Yodo , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Microscopía Electrónica de Transmisión , Nanocompuestos/ultraestructura , Nanotecnología , Difracción de Polvo , Tomografía Computarizada de Emisión de Fotón Único/métodos
9.
J Nanosci Nanotechnol ; 20(4): 2040-2044, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31492210

RESUMEN

We report the synthesis of 64Cu-labeled folate-conjugated magnetic nanoparticles for positron emission tomography (PET)/magnetic resonance imaging (MRI)-based diagnosis of cancer. The citrate/hydrazine-stabilized Fe3O4 nanoparticles measuring ~50 nm were utilized for target synthesis. Radio-thin-layer chromatography (TLC) analysis shows the formation of 64Cu-labeled nanomaterial with a radiochemical purity of 82.17% and a stability of ~90% in buffer solution and human serum for 24 h. Moreover, the sample exhibited good cellular uptake in breast (SKBR3), oral (KB) and lung (A549) cancer cell lines.


Asunto(s)
Nanopartículas , Neoplasias , Línea Celular Tumoral , Óxido Ferrosoférrico , Ácido Fólico , Humanos , Nanopartículas Magnéticas de Óxido de Hierro , Tomografía de Emisión de Positrones
10.
Biosens Bioelectron ; 142: 111511, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31319325

RESUMEN

Dengue virus is a mosquito-borne, single positive-stranded RNA virus that spread human being through infected female Aedes mosquito bite and causes dengue fever. The demand for early detection of this virus has increased to control the widespread of infectious diseases and protect humankind from its harmful effects. Recently, biosensors are found to the potential tool to detect and quantify the virus with fast detection, relatively cost-effective, high sensitivity and selectivity than the conventional diagnostic methods such as immunological and molecular techniques. Mostly, the biosensors employ electrochemical detection technique with transducers, owing to its easy construction, low-cost, ease of use, and portability. Here, we review the current trends and advancement in the electrochemical diagnosis of dengue virus and discussed various types of electrochemical biosensing techniques such as; amperometric, potentiometric, impedometric, and voltammetric sensing. Apart from these, we discussed the role of biorecognition molecules such as nucleic acid, antibodies, and lectins in electrochemical sensing of dengue virus. In addition, the review highlighted the benefits of the electrochemical approach in comparison with traditional diagnostic methods. We expect that these dengue virus diagnostic techniques will continue to evolve and grow in future, with exciting new possibilities stemming from advancement in the rational design of electrochemical biosensors.


Asunto(s)
Técnicas Biosensibles/instrumentación , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Técnicas Electroquímicas/instrumentación , Animales , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Diseño de Equipo , Humanos
11.
Nucl Med Biol ; 34(1): 117-20, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17210468

RESUMEN

The tandem target for a simultaneous production of [11C]CH4 and [(18)F]-fluoride has been designed and evaluated. A separate recovery system has been applied for a simultaneous collection of [11C]CH4 and [(18)F]-fluoride after a bombardment. The [11C]CH4 target was placed in front, and the [18F]-fluoride target was posted successively. An aluminum grid was employed between the two target cavities to improve the burst pressure of the titanium foil during an irradiation. It was demonstrated that a useful amount of [11C]CH4 and [18F]-fluoride can be produced simultaneously by this newly designed system.


Asunto(s)
Radioisótopos de Carbono/química , Radioisótopos de Flúor/química , Flúor/química , Marcaje Isotópico/métodos , Metano/química , Radiofármacos/síntesis química , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos
12.
Appl Radiat Isot ; 115: 8-12, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27295512

RESUMEN

A separation study using a (176)Yb target for the preparation of nca (177)Lu, which is a beta-emitting nuclide used not only in radioimmunotherapy applications but also in the treatment of various lesions, has been performed. A material having a better selectivity and separation efficiency for Lu than Yb was developed, and the separation conditions of (177)Lu were derived using this from a neutron irradiated (176)Yb target. The separation material was an organo-ceramic hybrid material containing a phosphate group. Adsorption behavior was determined through batch experiments, and (177)Lu separation from the Yb target was evaluated through column experiments. The Yb target, with a 99.72% in (176)Yb, was irradiated in the irradiation hole of HANARO, which has a thermal neutron flux of 1.6E+14ncm(-2)s(-1). The batch experiments revealed that the organo-ceramic hybrid material (Sol-POS) had a separation factor of 1.6 at 0.5M HCl. Separation was performed through extraction chromatography using a 5mg enriched Yb target, and the separation yield of the NCA (177)Lu was about 78%. If the amount of Yb target is increased to produce curies level (177)Lu, additional purification will be needed.


Asunto(s)
Lutecio/aislamiento & purificación , Radioisótopos/aislamiento & purificación , Radiofármacos/aislamiento & purificación , Adsorción , Quelantes , Cromatografía/métodos , Humanos , Lutecio/uso terapéutico , Neutrones , Radioisótopos/uso terapéutico , Radiofármacos/uso terapéutico , República de Corea , Tecnología Radiológica/instrumentación , Tecnología Radiológica/métodos , Iterbio/efectos de la radiación
13.
J Adv Res ; 7(6): 863-71, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27672449

RESUMEN

The present work focused on the synthesis of ß-chitosan submicron particles (CSPs) from Todarodes pacificus using mechanochemical techniques. The gladius was submitted to a sequence of mechanical and chemical treatments to synthesize ß-chitin (CT), which was further deacetylated to form spherical chitosan submicron particles with an average diameter of ⩽100 nm. The surface morphology of ß-chitin and CSPs was observed using electron microscopy. The degree of deacetylation (DD%), evaluated from the absorbance peak of a Fourier Transform Infrared (FTIR) spectrum, was 80 ± 2.5%. Physicochemical characterization exhibited good crystallinity, positive zeta potential and low molecular weight, as well as reduced ash content and high water-binding capacity. CSPs exhibit significant antimicrobial properties toward all tested pathogenic bacterial and fungal microorganisms. Antioxidant analysis revealed high reducing power and excellent scavenging and chelating ability. Hence, CSPs synthesized from gladius of Todarodes pacificus using mechanochemical techniques are promising candidates for biomedical applications.

14.
Exp Mol Med ; 37(4): 269-75, 2005 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-16155403

RESUMEN

The antiarrhythmic clofilium is an efficient blocker of hERG1 potassium channels that are strongly expressed in the heart. Therefore, derivatives of clofilium that emit positrons might be useful tools for monitoring hERG1 channels in vivo. Fluoro- clofilium (F-clofilium) was synthesized and its channel-blocking properties were determined for hERG1 and hEAG1 channels expressed in HEK?293 cells and in Xenopus oocytes. When applied extracellularly in the whole-cell patch-clamp configuration, F-cloflium exhibited a slower onset of block when compared with clofilium, presumably owing to its lower membrane permeability. When applied in the inside-out configuration at the intracellular membrane side, it blocked hEAG1 channels almost as efficiently as clofilium (IC50 1.37 nM and 0.83 nM, respectively). Similar results were obtained for hERG1, showing F-clofilium is a potent hERG1 and hEAG1 channel blocker once it has reached the intracellularly accessible target site at the channel. Using the (18)F-labeled analog we studied the in vivo binding and distribution of F-clofilium in mice and a dog. Greatest activity was found in kidneys and bones. A small but significant enrichment of activity in the dog myocardium known for its expression of cERG1 channels allowed to depict the myocardium of a living dog by PET. Thus, F-clofilium is a useful tool for imaging hERG channels in living organisms.


Asunto(s)
Antiarrítmicos/farmacología , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Tomografía de Emisión de Positrones , Bloqueadores de los Canales de Potasio/farmacología , Animales , Antiarrítmicos/farmacocinética , Línea Celular , Perros , Canal de Potasio ERG1 , Electrones , Femenino , Concentración 50 Inhibidora , Riñón/metabolismo , Ratones , Ratones Endogámicos BALB C , Miocardio/metabolismo , Bloqueadores de los Canales de Potasio/farmacocinética , Compuestos de Amonio Cuaternario/farmacocinética , Compuestos de Amonio Cuaternario/farmacología , Distribución Tisular , Xenopus
15.
ACS Appl Mater Interfaces ; 7(24): 13405-14, 2015 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-26010272

RESUMEN

Flexible supercapacitor electrodes have been fabricated by simple fabrication technique using graphite nanoflakes on polymer lapping films as flexible substrate. An additional thin layer of conducting polymer polypyrrole over the electrode improved the surface conductivity and exhibited excellent electrochemical performances. Such capacitor films showed better energy density and power density with a maximum capacitance value of 37 mF cm(-2) in a half cell configuration using 1 M H2SO4 electrolyte, 23 mF cm(-2) in full cell, and 6 mF cm(-2) as planar cell configuration using poly(vinyl alcohol) (PVA)/phosphoric acid (H3PO4) solid state electrolyte. Moreover, the graphite nanoflakes/polypyrrole over polymer lapping film demonstrated good flexibility and cyclic stability.

16.
Bioelectrochemistry ; 104: 44-50, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25727854

RESUMEN

An effective enzymatic glucose biosensor was developed by immobilizing glucose oxidase on chitosan submicron particles synthesized from the gladius of Todarodes pacificus (GCSP). The chemically synthesized chitosan from gladius was pulverized to submicron particles by ball milling technique, which was further characterized and compared with the standard chitosan (SCS). The degree of deacetylation of GCSP was determined using FTIR spectroscopy which was comparable to the value of standard chitosan. The glucose oxidase (GOx) was immobilized over GCSP on porous zinc oxide/platinum nanoparticle (ZnO/Pt) based electrode. The morphological and structural properties of the electrodes were analyzed using scanning electron microscopy and X-ray diffraction analysis. The glucose sensing behavior of electrode was estimated using electrochemical analysis and showed an excellent analytical performance. The electrode ZnO/Pt/GCSP conjugated with GOx displayed high sensitivity (88.76 µA mM(-1) cm(-2)) with low detection limit in short response time. In addition, the very low value of Michaelis-Menten constant for GCSP based electrode contributes a better affinity of the electrode surface towards glucose oxidase.


Asunto(s)
Técnicas Biosensibles/métodos , Quitosano/química , Decapodiformes/química , Enzimas Inmovilizadas/química , Glucosa Oxidasa/química , Glucosa/análisis , Tamaño de la Partícula , Animales , Técnicas Biosensibles/instrumentación , Electroquímica , Electrodos , Enzimas Inmovilizadas/metabolismo , Glucosa Oxidasa/metabolismo , Platino (Metal)/química , Óxido de Zinc/química
17.
Appl Radiat Isot ; 85: 96-100, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24393812

RESUMEN

This study described an effective method to load (125)I on silver rods for the preparation of a brachytherapy source. We tested various ligands on the silver rod surface to screen the one with the highest adsorption and specific radioactivity. In addition, we investigated the effect of surface etching to increase the adsorption capability followed by the extended surface area. We also found that the use of an oxidant during iodide adsorption can increase the loading significantly. The maximum activity of 137.90MBq/rod (3.7269mCi/rod) was achieved on the etched silver rods with phosphate ligand and hydrogen peroxide as an oxidant. In addition, this is 4.5-fold higher than that of the conventional chloride treatment method.


Asunto(s)
Braquiterapia/métodos , Radioisótopos de Yodo/administración & dosificación , Radiofármacos/administración & dosificación , Plata , Adsorción , Humanos , Oxidantes , Propiedades de Superficie
18.
Nucl Med Biol ; 39(7): 1093-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22575270

RESUMEN

INTRODUCTION: Established radiotracers for positron emission tomography (PET) myocardial perfusion study are commonly labeled with short-lived radio-isotopes that limit their widespread clinical use. Thus, we synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)tris(4-methoxyphenyl)phosphonium salt ([(18)F]FETMP) as a novel myocardial perfusion agent that penetrates the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to the negative inner-transmembrane potentials. METHODS: The [(18)F]FETMP was synthesized via two-step nucleophilic substitution reactions of no-carrier-added [(18)F]fluoride with the precursor 2,2'-oxybis(ethane-2,1-diyl)bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K(2)CO(3). The [(18)F]FETMP accumulation was measured in cell culture with rat embryonic cardiomyoblast (H9c2) and mouse normal fibroblast (NIH/3T3) cell lines. The mitochondrial membrane potential-dependent cellular uptake of [(18)F]FETMP was further assessed using the H9c2 cells treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) which is a protonophore that selectively abolishes the mitochondrial membrane potential. Biodistribution and micro-PET studies were performed in normal BALB/c mice to test and optimize the kinetics for radiolabeled phosphonium cation. RESULTS: The radiolabeled compound was synthesized with 10%-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >5.92TBq/µmol. The cellular uptake assay showed preferential uptake of [(18)F]FETMP in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]FETMP in mice and rats showed preferential accumulation in the myocardium. CONCLUSIONS: The results suggest that [(18)F]FETMP would be a promising candidate for myocardial imaging and might be useful for clinical cardiac PET/CT applications.


Asunto(s)
Anisoles/síntesis química , Radioisótopos de Flúor , Corazón/diagnóstico por imagen , Compuestos Organofosforados/síntesis química , Tomografía de Emisión de Positrones/métodos , Animales , Anisoles/metabolismo , Anisoles/farmacocinética , Transporte Biológico , Técnicas de Química Sintética , Interacciones Hidrofóbicas e Hidrofílicas , Marcaje Isotópico , Masculino , Ratones , Compuestos Organofosforados/metabolismo , Compuestos Organofosforados/farmacocinética , Radioquímica , Ratas
19.
J Nucl Med ; 53(11): 1779-85, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23038748

RESUMEN

UNLABELLED: Radiolabeled lipophilic cationic compounds, such as (18)F-labeled phosphonium salt, accumulate in the mitochondria through a negative inner transmembrane potential. The purpose of this study was to develop and evaluate ((18)F-fluoropentyl)triphenylphosphonium salt ((18)F-FPTP) as a myocardial PET agent. METHODS: A reference compound of (18)F-FPTP was synthesized via 3-step nucleophilic substitution reactions and was radiolabeled via 2-step nucleophilic substitution reactions of no-carrier-added (18)F-fluoride. Accumulations of (18)F-FPTP, (3)H-tetraphenylphosphonium, and (99m)Tc-sestamibi were compared in a cultured embryonic cardiomyoblast cell line (H9c2). The biodistribution of (18)F-FPTP was assessed using BALB/c mice. The (18)F-FPTP small-animal PET study was performed in Sprague-Dawley rats with or without left coronary artery (LCA) ligation. RESULTS: (18)F-FPTP was synthesized with a radiochemical yield of 15%-20% and radiochemical purity of greater than 98%. Specific activity was greater than 6.3 TBq/µmol. Cell uptake of (18)F-FPTP was more than 15-fold higher in H9c2 than in normal fibroblasts (human normal foreskin fibroblasts). Selective collapse of mitochondrial membrane potential substantially decreased cellular uptake for (18)F-FPTP and (3)H-tetraphenylphosphonium, compared with that for (99m)Tc-sestamibi. The biodistribution data in mice (n = 24) showed rapid blood clearance and high accumulation in the heart. Heart-to-blood ratios at 10 and 30 min were 54 and 133, respectively. Heart-to-lung and heart-to-liver ratios at 10, 30, and 60 min were 4, 4, and 7 and 4, 5, and 7, respectively. Dynamic small-animal PET for 60 min after injection of (18)F-FPTP showed an initial spike of radioactivity, followed by retention in the myocardium and rapid clearance from the background. (18)F-FPTP small-animal PET images in LCA-occluded rats demonstrated sharply defined myocardial defects in the corresponding area of the myocardium. The myocardial defect size measured by (18)F-FPTP small-animal PET correlated closely with the hypoperfused area measured by quantitative 2,3,5-triphenyltetrazolium chloride staining (r(2) = 0.92, P < 0.001). CONCLUSION: The excellent pharmacokinetics of (18)F-FPTP and its correlation with 2,3,5-triphenyltetrazolium chloride staining in normal and LCA-occluded rats suggest that this molecular probe may have a high potential as a mitochondrial voltage sensor for PET. This probe may also allow high throughput, with multiple daily studies and a wide distribution of PET myocardial imaging in the clinic.


Asunto(s)
Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Mitocondrias/patología , Infarto del Miocardio/patología , Compuestos Organofosforados/metabolismo , Fosfinas/metabolismo , Animales , Transporte Biológico , Línea Celular , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Mitocondrias/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagen , Compuestos Organofosforados/síntesis química , Compuestos Organofosforados/farmacocinética , Fosfinas/síntesis química , Fosfinas/farmacocinética , Tomografía de Emisión de Positrones , Radioquímica , Ratas , Ratas Sprague-Dawley
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