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Coordination geometry-induced optical imaging of <scp>l</scp> -cysteine in cancer cells using imidazopyridine-based copper( <scp>ii</scp> ) complexes
摘要： Overexpression of cysteine cathepsins proteases has been documented in a wide variety of cancers, and enhances the L-cysteine concentration in tumor cells. We report the synthesis and characterization of copper(II) complexes [Cu(L1)2(H2O)](SO3CF3)2, 1, L1 = 3-phenyl-1-(pyridin-2-yl)imidazo[1,5-a]pyridine, [Cu(L2)2(SO3CF3)]SO3CF3, 2, L2 = 3-(4-methoxyphenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine, [Cu(L3)2(H2O)](SO3CF3)2, 3, L3 = 3-(3,4-dimethoxy-phenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine and [Cu(L4)2(H2O)](SO3CF3)2, 4, L4 = dimethyl-[4-(1-pyridin-2-yl-imidazo[1,5-a]pyridin-3-yl)phenyl]amine as 'turn-on' optical imaging probes for L-cysteine in cancer cells. The molecular structure of complexes adopted distorted trigonal pyramidal geometry (τ, 0.68–0.87). Cu–Npy bonds (1.964–1.989 ?) were shorter than Cu–Nimi bonds (2.024–2.074 ?) for all complexes. Geometrical distortion was strongly revealed in EPR spectra, showing gk (2.26–2.28) and Ak values (139–163 × 10?4 cm?1) at 70 K. The d–d transitions appeared around 680–741 and 882–932 nm in HEPES, which supported the existence of five-coordinate geometry in solution. The Cu(II)/Cu(I) redox potential of 1 (0.221 V vs. NHE) was almost identical to that of 2 and 3 but lower than that of 4 (0.525 V vs. NHE) in HEPES buffer. The complexes were almost non-emissive in nature, but became emissive by the interaction of L-cysteine in 100% HEPES at pH 7.34 via reduction of Cu(II) to Cu(I). Among the probes, probe 2 showed selective and efficient turn-on fluorescence behavior towards L-cysteine over natural amino acids with a limit of detection of 9.9 × 10?8 M and binding constant of 2.3 × 105 M?1. The selectivity of 2 may have originated from a nearly perfect trigonal plane adopted around a copper(II) center (～120.70°), which required minimum structural change during the reduction of Cu(II) to Cu(I) while imaging Cys. The other complexes, with their distorted trigonal planes, required more reorganizational energy, which resulted in poor selectivity. Probe 2 was employed for optical imaging of L-cysteine in HeLa cells and macrophages. It exhibited brighter fluorescent images by visualizing Cys at pH 7.34 and 37 °C. It showed relatively less toxicity for these cell lines as ascertained by the MTT assay.
关键词： optical imaging,cancer cells,turn-on fluorescence,imidazopyridine,L-cysteine,Copper(II) complexes
更新于2025-11-21 11:08:12
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Characterization of a non-contact imaging scintillator-based dosimetry system for total skin electron therapy
摘要： Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick x 15 mm) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied. The effect of varying scintillator diameter and thickness on light output was evaluated. Furthermore, the scintillator emission spectra and impact of dosimeter thickness on surface dose were also quantified. Since the scintillators were custom-machined, dosimeter-to-dosimeter variation was tested. Scintillator surface dose measurements were compared to those obtained by optically stimulated luminescence dosimeters (OSLD). Light output from scintillator dosimeters evaluated in this study was insensitive to radiation damage, temperature, and dose rate. Maximum wavelength of emission was found to be 422 nm. Dose reported by scintillators was linearly related to that from OSLDs. Build-up from placement of scintillators and OSLDs had a similar effect on surface dose (3.9% increase). Variation among scintillator dosimeters was found to be 0.3 ± 0.2%. Scintillator light output increased linearly with dosimeter thickness (~1.9×/mm). All dosimeter diameters tested were able to accurately measure surface dose. Scintillator dosimeters can potentially improve surface dosimetry-associated workflow for TSET in the radiation oncology clinic. Since scintillator data output can be automatically recorded to a patient medical record, the chances of human error in reading out and recording surface dose are minimized.
关键词： non-contact,surface dosimetry,optical imaging,scintillator,remote
更新于2025-11-14 15:30:11
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Modern description of Rayleigh's criterion
摘要： Rayleigh’s criterion states that it becomes essentially difficult to resolve two incoherent optical point sources separated by a distance below the width of point spread functions (PSFs), namely, in the subdiffraction limit. Recently, researchers have achieved superresolution for two incoherent point sources with equal strengths, surpassing Rayleigh’s criterion. However, situations where more than two point sources needed to be resolved have not been fully investigated. Here we prove that for any incoherent sources with arbitrary strengths, a one- or two-dimensional (1D or 2D) image can be precisely resolved up to its second moment in the subdiffraction limit, i.e., the Fisher information (FI) is nonzero. But the FI with respect to higher order moments always tends to zero polynomially as the size of the image decreases, for any type of nonadaptive measurement. We call this phenomenon a modern description of Rayleigh’s criterion. For PSFs under certain constraints, the optimal measurement basis estimating all moments in the subdiffraction limit for 1D weak-source imaging is constructed. Such a basis also generates the optimal-scaling FI with respect to the size of the image for 2D or strong-source imaging, which achieves an overall quadratic improvement compared to direct imaging.
关键词： Fisher information,optical imaging,Rayleigh's criterion,superresolution,incoherent sources,subdiffraction limit
更新于2025-09-23 15:23:52
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Magneto-optical imaging characteristics of weld defects under alternating and rotating magnetic field excitation
摘要： This paper mainly examines the characteristics of magneto-optical (MO) images of weld defects under alternating and rotating magnetic field excitation. Weld defects including surface and subsurface defects were subjected to magneto-optical imaging (MOI) nondestructive testing (NDT) experiments. The MO images of different weld defects under alternating magnetic field excitation and rotating magnetic field excitation have been compared to determine the best effect of nondestructive testing, and a cruciform welding seam was used to verify the detection effect of rotating magnetic field. Besides, the values of standard deviation and maximum difference have been determined to analyze the difference in the effects of two magnetic fields, and image processing methods were applied to extract defect information, such as histogram equalization. Experimental results show that the optimal excitation voltage and lift-off value of rotating magnetic field are 120 V and 20 mm, respectively; image histogram equalization can significantly improve the contrast of MO images, and there is a distinct difference in the detection effect of two magnetic fields. Under the same excitation conditions, the detection effect of rotating magnetic fields is always better than the effect of alternating magnetic fields, and rotating magnetic field excitation has obvious advantages in detecting multidirection and subsurface defects in that the detection depth can reach about 8 mm.
关键词： Magneto-optical imaging,Electromagnetic optics,Nondestructive testing,Rotating magnetic field
更新于2025-09-23 15:23:52
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Enhanced image processing and archiving capabilities of magneto-optical imaging for non-destructive evaluation
摘要： In its current state, the wide acceptance of the Magneto-Optical Imaging (MOI) technique is hindered due to noise, lack of recordable results, and impossibility of data post-processing. This paper presents some add-ons made to a commercial MOI system to ease the image interpretation, archiving and reporting of the results. In addition, a few image processing techniques are also employed in an attempt to perform automatic flaw detection. The recording capability of the MOI instrument output images was addressed by digitizing the video signal in video or image files. To help with the identification of the damage location and distance between images, a rotary quadrature encoder was mounted onto the MOI scan head. The use of the encoder allowed the identification of the inspection location with respect to a reference position, such as the beginning of the scan. Moreover, it allowed saving images at fixed intervals, which were then stitched into a single image, thus simplifying the post inspection analysis process. Both live and post-inspection image processing capabilities were made available. Implemented image processing included background subtraction, de-noising, contrast adjustment and morphological operation, among others. Contrast stretching transform and background subtractions were found to be among the most powerful techniques that could be used in simplifying the image interpretation.
关键词： non-destructive evaluation,Magneto-optical imaging,image processing
更新于2025-09-23 15:23:52
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Rapid Multisite Remote Surface Dosimetry for Total Skin Electron Therapy: Scintillator Target Imaging
摘要： Verifying radiation-field uniformity in total skin electron therapy is important to ensuring adequate and effective treatment administration. This clinical study presents a novel, scintillation-based, optical-imaging technique for conducting surface dosimetry in patients undergoing total skin electron therapy. The system exceeded the ease of use of established dosimetry techniques at a similar level of accuracy.
关键词： total skin electron therapy,optical imaging,surface dosimetry,scintillator,remote dosimetry
更新于2025-09-23 15:23:52
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Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues
摘要： We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69 cancer tissues removed from the colons of normal and orthotopic mouse models of human colorectal cancer, respectively, demonstrated that the nanobeacon detected colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with colorectal tumors. Histological evaluation revealed that 9 patients suffered from cancer and the rest had adenoma. Mean fluorescence intensities of tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in cancer patients with a high probability (89%); however, the probability reduced to 50% in adenoma patients. There was a reasonable likelihood for diagnosis of colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.
关键词： Colorectal cancer,Diagnostic agent,Optical imaging,Peanut agglutinin,Biomarker imaging,Nanosphere,Thomsen-Friedenreich antigen
更新于2025-09-23 15:22:29
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A novel bioreactor for combined magnetic resonance spectroscopy and optical imaging of metabolism in 3D cell cultures
摘要： Purpose: Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized 13C‐pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures. Methods: The model fitting for FLIM data analysis and the theory behind a model for the diffusion of pyruvate into a collagen gel are detailed. The device is MRI‐compatible, including an optical window, a temperature control system and an injection port for the introduction of contrast agents. Three‐dimensional printing, computer numerical control machining and laser cutting were used to fabricate custom parts. Results: Performance of the bioreactor is demonstrated for 4 T1 murine breast cancer cells under glucose deprivation. Mean nicotinamide adenine dinucleotide (NADH) fluorescence lifetimes were 10% longer and hyperpolarized 13C lactate:pyruvate (Lac:Pyr) ratios were 60% lower for glucose‐deprived 4 T1 cells compared to 4 T1 cells in normal medium. Looking at the individual components of the NADH fluorescent lifetime, τ1 (free NADH) showed no significant change, while τ2 (bound NADH) showed a significant increase, suggesting that the increase in mean lifetime was due to a change in bound NADH. Conclusion: A novel bioreactor that is compatible with, and can exploit the benefits of, both FLIM and 13C MRS in 3D cell cultures for studies of cell metabolism has been designed and applied.
关键词： multimodal,optical imaging,bioreactor,magnetic resonance spectroscopy (MRS),nicotinamide adenine dinucleotide (NADH),metabolism,fluorescence lifetime imaging (FLIM),lactate production
更新于2025-09-23 15:22:29
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Roadmap for the development and GMP translation of optical tracers cetuximab-800CW and trastuzumab-800CW
摘要： Optical molecular imaging using fluorescently labeled monoclonal antibodies is of significant added value to guide surgical or endoscopic procedures. However, development of tracers for clinical trials is complex, and therefore implementation in the clinic is slow. We present a roadmap for development and translation of monoclonal antibody tracers into a current Good Manufacturing Process (cGMP) compliant drug product. Methods. The production process of cetuximab-800CW and trastuzumab-800CW was optimized with regard to dye to protein label ratio and formulation buffer. Promising formulations were produced under cGMP conditions and advanced to full-scale stability study. Tracers were analyzed for stability by SE-HPLC, pH-measurement, osmolality, visual inspection and sterility, as required by the European Pharmacopeia and cGMP guidelines. Results. For cetuximab-800CW, 7 formulations were investigated and for trastuzumab-800CW 10 formulations were investigated. Based on the formulation study results, we chose 2 formulations per antibody for investigation during full-scale stability study. These formulations all performed well, showing good compliance with the acceptance criteria set for each product. Conclusion We designed a roadmap to standardize the development, formulation and cGMP translation of molecular fluorescent tracers. Using our standardized approach, we developed two stable antibody-based tracers for clinical use. When developing tracers, the proposed roadmap can be used to efficiently develop a cGMP compliant formulation and improve translation of newly developed optical tracers to first in human use.
关键词： optical imaging,cGMP,development,roadmap
更新于2025-09-23 15:22:29
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Amphiphilic nanoaggregates with bimodal MRI and optical properties exhibiting magnetic field dependent switching from positive to negative contrast enhancement
摘要： Mixed micelles based on amphiphilic gadolinium(III)-DOTA and europium(III)-DTPA complexes were synthesized and evaluated for their paramagnetic and optical properties as potential bimodal contrast agents. Amphiphilic folate molecule for targeting the folate receptor protein, which is commonly expressed on the surface of many human cancer cells, was used in the self-assembly process in order to create nanoaggregates with targeting properties. Both targeted and non-targeted nanoaggregates formed mono-disperse micelles having distribution maxima of 10 nm. The micelles show characteristic europium(III) emission with quantum yields of 2% and 1.1% for the non-targeted and targeted micelles respectively. Fluorescence microscopy using excitation at 405 nm and emission at 575-675 nm was employed to visualize nanoaggregates in cultured HeLa cells. The uptake of folate-targeted and non-targeted micelles is already visible after 5 hour incubation, and was characterized with the europium(III) emission which is clearly observable in the cytoplasm of the cells. The very fast longitudinal relaxivity r1 of ca. 26 s-1 mM-1 per gadolinium(III) ion was observed for both micelles at 60 MHz and 310 K. Upon increasing the magnetic field to 300 MHz the nanoaggregates exhibited a large switching to transversal relaxivity with r2 value of ca. 52 s-1 mM-1 at 310 K. Theoretical fitting of the 1H NMRD profiles indicate that the efficient T1 and T2 relaxations are sustained by the favorable magnetic and electron-configuration properties of the gadolinium(III) ion, rotational correlation time and coordinated water molecule. These nanoaggregates could have versatile application as a positive contrast agent at currently used magnetic imaging field strengths and a negative contrast agent in higher field applications, while at the same time offering the possibility for the loading of hydrophobic therapeutics or targeting molecules.
关键词： bimodal contrast agents,gadolinium,nanoaggregates,optical imaging,micelle,high field MRI
更新于2025-09-23 15:22:29