RESUMEN
Drug development includes imaging agents, contrast agents and radiopharmaceuticals; these materials differ from therapeutic drugs in that they are largely used to diagnose and/or monitor diseases and not treat them. Consequently, nonclinical safety testing needs are different. An examination of testing packages supporting clinical entry and/or marketing of these materials has shown a common approach to some study types (eg, imaging, biodistribution and toxicity testing). Recent regulatory guidelines to support development are the United States Food and Drug Administration (FDA)'s "Guidance for Industry Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations" and the European Medicines Agency (EMA)'s "Guideline on the Non-Clinical Requirements for Radiopharmaceuticals" (currently draft). It is hoped that these documents will allow developers to only perform nonclinical studies that are necessary to support functionality, follow distribution of the material and examine general safety/toxicity. However, as they are mainly focused on radiopharmaceuticals, companies are likely to apply knowledge of established testing packages to other new imaging agents and/or follow principles given in older regulatory guidelines, namely FDA's "Guidance for Industry Developing Medical Imaging Drug and Biological Products Part I Conducting Safety Assessments". Thus, in some cases, the need for regulatory agency interaction is still vital to avoid development surprises and delays due to an incomplete or badly performed testing package.
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Seguridad Química , Medios de Contraste/toxicidad , Usos Diagnósticos de Compuestos Químicos , Monitoreo de Drogas/métodos , Radiofármacos/toxicidad , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
We report 2 cases of drug induced Parkinsonism followed longitudinally that remained symptomatic 22 and 27 months after stopping causative agents with normal dopamine ioflupane iodine-123 (DaT) single-photon emission computed tomography (SPECT) scans at 8 and 16 months.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedad de Parkinson Secundaria , Tranquilizantes/efectos adversos , Adulto , Anciano , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Estudios Longitudinales , Masculino , Nortropanos , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Enfermedad de Parkinson Secundaria/metabolismo , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE. The purpose of this article is to provide a review of 123I-ioflupane SPECT in the evaluation of suspected parkinsonian syndromes (PSs). This collection of diseases presents frequent diagnostic challenges, even by movement disorder and dementia specialists. CONCLUSION. The 123I-ioflupane scan serves as an imaging biomarker of the status of presynaptic dopamine transporters (DATs) in the striatum. As a result of neuronal death, DATs are greatly reduced in patients with PS neurodegenerative disorders, whereas clinical mimics generally do not show striatal DAT loss. This provides a tremendous opportunity for 123I-ioflupane to aid in the accurate and timely diagnosis of these patients and optimize their management.
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Cuerpo Estriado/diagnóstico por imagen , Usos Diagnósticos de Compuestos Químicos , Nortropanos , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Humanos , Radioisótopos de Yodo , RadiofármacosRESUMEN
PURPOSE: Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. METHODS: A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. RESULTS: The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. CONCLUSIONS: Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.
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Lavado Gástrico/métodos , Gastroscopía/métodos , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lactato de RingerRESUMEN
Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate-severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate-severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken together, our results suggest that the dopaminergic system is affected by a moderate-severe traumatic brain injury in a significant proportion of patients, even in the absence of clinical motor parkinsonism. Reduced dopamine transporter levels are most commonly seen in the caudate and this is likely to reflect the pattern of nigrostriatal tract damage produced by axonal injury and associated midbrain damage.
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Lesiones Traumáticas del Encéfalo/patología , Encéfalo/diagnóstico por imagen , Dopamina/metabolismo , Adulto , Anciano , Encéfalo/efectos de los fármacos , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Nortropanos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
The development of imaging agents was initially driven following the discovery of X-ray technologies, but quickly evolved and expanded to include radiolabeling of cells and tissues to assist disease diagnosis and progression. The first imaging agents preceded the Great War but the field did not gain momentum until the 1950s. The approval rate for imaging NMEs continued at a high level for the remainder of the 20th century, but substantially decreased thereafter. This decline in approval rates corresponds with industry consolidation. Such losses have stabilized, but could have important implications for a field that has conveyed direct benefits to medicine and that could ensure the future of the wider biopharmaceutical industry.
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Usos Diagnósticos de Compuestos Químicos , Aprobación de Drogas , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
INTRODUCTION: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL. OBJECTIVE: To radiolabel rituximab with technetium-99m (99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL. METHODS: Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h. RESULTS: Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice. CONCLUSIONS: Our results support the potential use of rituximab labeled either with 99mTc or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation.
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Carbocianinas , Linfoma no Hodgkin/diagnóstico por imagen , Imagen Molecular/métodos , Rituximab , Tecnecio , Animales , Antígenos CD20/metabolismo , Carbocianinas/farmacocinética , Línea Celular Tumoral , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Ratones Endogámicos BALB C , Radiofármacos/metabolismo , Radiofármacos/farmacocinética , Rituximab/química , Rituximab/metabolismo , Rituximab/farmacocinética , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Tecnecio/farmacocinética , Distribución TisularRESUMEN
There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4-1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology.
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Usos Diagnósticos de Compuestos Químicos , Mediciones del Volumen Pulmonar/métodos , Nanopartículas , Administración por Inhalación , Aerosoles , Difusión , Humanos , Pulmón/patología , Imagen por Resonancia Magnética , Tamaño de la Partícula , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Respiración , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted therapies. Herein, we report a highly specific peptide-based positron emission tomography (PET) imaging agent for PD-L1. We assessed the binding modes of the peptide WL12 to PD-L1 by docking studies, developed a copper-64 labeled WL12 ([64Cu]WL12), and performed its evaluation in vitro, and in vivo by PET imaging, biodistribution and blocking studies. Our results show that [64Cu]WL12 can be used to detect tumor PD-L1 expression specifically and soon after injection of the radiotracer, to fit within the standard clinical workflow of imaging within 60 min of administration.
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Antígeno B7-H1/análisis , Neoplasias/metabolismo , Péptidos/metabolismo , Péptidos/farmacocinética , Tomografía de Emisión de Positrones/métodos , Animales , Antígeno B7-H1/metabolismo , Células CHO , Radioisótopos de Cobre/administración & dosificación , Radioisótopos de Cobre/farmacocinética , Cricetulus , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Ratones SCID , Simulación del Acoplamiento Molecular , Neoplasias/diagnóstico por imagen , Péptidos/administración & dosificación , Receptor de Muerte Celular Programada 1/metabolismo , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P<0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer.
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Antígenos de Superficie/metabolismo , Aptámeros de Nucleótidos/química , Glutamato Carboxipeptidasa II/metabolismo , Nanoestructuras/administración & dosificación , Neoplasias de la Próstata/diagnóstico por imagen , Ultrasonografía/métodos , Animales , Antígenos de Superficie/genética , Carbocianinas/farmacocinética , Línea Celular Tumoral , Medios de Contraste/farmacocinética , Usos Diagnósticos de Compuestos Químicos , Glutamato Carboxipeptidasa II/genética , Humanos , Lípidos/química , Masculino , Ratones Desnudos , Nanoestructuras/química , Tamaño de la Partícula , Polietilenglicoles/química , Ultrasonografía Doppler en Color/métodos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Dendrimers are large polymeric structures with nanosize dimensions (1-10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific "architecture" and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases.
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Dendrímeros/administración & dosificación , Dendrímeros/farmacología , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , Administración Oral , Antibacterianos/administración & dosificación , Antibacterianos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Dendrímeros/química , Usos Diagnósticos de Compuestos Químicos , Interacciones Farmacológicas , Oftalmopatías/tratamiento farmacológico , Técnicas de Transferencia de Gen , Humanos , Polímeros/químicaRESUMEN
Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a (18)F-labeled PDE10A imaging agent for positron emission tomography. The use of ortho-fluoropyridines as residues could potentially enable the introduction of (18)F through nucleophilic substitution for radiolabeling purposes. 2-Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule. The reference compounds, 1,8-dipyridinylimidazo[1,5-a]quinoxalines and 1-pyridinylimidazo[1,5-a]quinoxalines, show inhibitory potencies at best in the subnanomolar range and selectivity factors greater than 38 against other PDE's. 1,8-Dipyridinylimidazo[1,5-a]quinoxalines are more potent inhibitors than 1-pyridinylimidazo[1,5-a]quinoxalines. Using 2-fluoro-3-pyridinyl as residue provided the most potent inhibitors 16 (IC50 = 0.12 nM), 17 (IC50 = 0.048 nM) and 32 (IC50 = 0.037 nM).
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Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/metabolismo , Quinoxalinas/química , Bromo/química , Técnicas de Química Sintética , Usos Diagnósticos de Compuestos Químicos , Evaluación Preclínica de Medicamentos , Humanos , Concentración 50 Inhibidora , Tomografía de Emisión de Positrones/métodos , Relación Estructura-ActividadRESUMEN
BACKGROUND: Upper gastrointestinal endoscopy (UGI-ES) and double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) are two major image-based methods to diagnose atrophic gastritis, which is mostly induced by Helicobacter pylori infection. However, there have been few studies directly comparing them. METHODS: Atrophic gastritis was evaluated using the data of 962 healthy subjects who underwent UGI-ES and UGI-XR within 1 year. RESULTS AND CONCLUSION: Based on UGI-ES and UGI-XR, 602 subjects did not have atrophic gastritis and 254 subjects did have it. Considering UGI-ES-based atrophic gastritis as the standard, sensitivity and specificity of UGI-XR-based atrophic gastritis were 92.0 % (254/276) and 92.8 % (602/649), respectively. The seven-grade Kimura-Takemoto classification of UGI-ES-based atrophic gastritis showed a strong and significant association with the four-grade UGI-XR-based atrophic gastritis. Sensitivity and specificity of serum anti-Helicobacter pylori IgG to detect UGI-ES/UGI-XR-based atrophic gastritis were 89.4 % (227/254) and 99.8 % (601/602), indicating that atrophic gastritis can be overlooked according to serum anti-Helicobacter pylori IgG alone.
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Endoscopía Gastrointestinal/métodos , Gastritis Atrófica/diagnóstico por imagen , Infecciones por Helicobacter/sangre , Inmunoglobulina G/sangre , Radiografía Abdominal/métodos , Adulto , Anciano , Bario , Medios de Contraste , Usos Diagnósticos de Compuestos Químicos , Gastritis Atrófica/inmunología , Gastritis Atrófica/microbiología , Tracto Gastrointestinal/diagnóstico por imagen , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/inmunología , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Rayos X , Adulto JovenRESUMEN
A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (⩽1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 °C, whereas a decrease in affinity (⩾10-fold) was observed with compound 26. The logP7.4 values of [(18)F]26-[(18)F]29 were in the range of â¼2.2-2.8 and microPET evaluation of [(18)F]26-[(18)F]29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [(18)F]28, [(18)F]28-d8, and [(18)F]29 was attributed to a combination of [(18)F]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [(18)F]26 and [(18)F]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [(18)F]fluoride.
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Radioisótopos de Flúor/química , Marcaje Isotópico/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/química , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Animales , Unión Competitiva , Técnicas de Química Sintética , Usos Diagnósticos de Compuestos Químicos , Radioisótopos de Flúor/farmacocinética , Humanos , Ligandos , Macaca fascicularis , Masculino , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Ratas Sprague-DawleyAsunto(s)
Alergia e Inmunología , Usos Diagnósticos de Compuestos Químicos , Hipersensibilidad a las Drogas/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Pruebas Inmunológicas/métodos , Preparaciones Farmacéuticas , Femenino , Humanos , MasculinoAsunto(s)
Alergia e Inmunología , Usos Diagnósticos de Compuestos Químicos , Hipersensibilidad a las Drogas/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Pruebas Inmunológicas/métodos , Preparaciones Farmacéuticas , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Tumor-target fluorescence bioimaging is an important means of early diagnosis, metal nanoclusters have been used as an excellent fluorescent probe for marking tumor cells due to their targeted absorption. We have developed a new strategy for facile synthesis of Au/Ce nanoclusters (NCs) by doping trivalent cerium ion into seed crystal growth process of gold. Au/Ce NCs have bright fluorescence which could be used as fluorescent probe for bioimaging. RESULTS: In this study, we synthesized fluorescent Au/Ce NCs through two-step hydrothermal reaction. The concentration range of 25-350 µM, Au/Ce NCs have no obvious cell cytotoxicity effect on HeLa, HepG2 and L02 cells. Furthermore, normal cells (L02) have no obvious absorption of Au/Ce NCs. Characterization of synthesized Au/Ce NCs was done by using TEM, EDS and XPS. Then these prepared Au/Ce NCs were applied for in vitro/in vivo tumor-target bioimaging due to its prolonged fluorescence lifetime and bright luminescence properties. CONCLUSIONS: The glutathione stabilized Au/Ce NCs synthesized through hydrothermal reaction possess stable and bright fluorescence that can be readily utilized for high sensitive fluorescence probe. Our results suggest that Au/Ce NCs are useful candidate for in vitro/in vivo tumor bioimaging in potential clinical application.
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Colorantes Fluorescentes/análisis , Colorantes Fluorescentes/química , Oro/química , Imagen Molecular/métodos , Nanocompuestos/química , Animales , Cerio/química , Usos Diagnósticos de Compuestos Químicos , Femenino , Colorantes Fluorescentes/farmacocinética , Glutatión/química , Células HeLa/efectos de los fármacos , Células Hep G2/efectos de los fármacos , Humanos , Nanopartículas del Metal/química , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Espectroscopía de Fotoelectrones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Asymptomatic, early-stage, cancer detection is a problem in the small intestine, that is largely inaccessible. This paper presents a cost-effective screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. The presented mixed-signal system has a small size, consumes little power and works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine, rather than collecting images that need labour intensive video analysis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.