13 research outputs found

    Kinetic analysis of coal and biomass co-gasification with carbon dioxide

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    Based on Thermogravimetric Analysis (TGA) experimental data, a kinetic analysis of the Boudouard reaction was studied for three different coal chars, three different biomass chars, and their mixtures. The coal chars included: North Dakota Lignite, Illinois No.6, and Powder River Basin char; the biomass chars included: Hardwood, Switchgrass, and Corn Stove char. The reaction temperature ranged from 900°C to 1100°C. Different kinetic models were used for modeling the reaction rate. For the simplified Dutta and Wen model, it was found that the reaction rate was first order with respect to both CO2 and carbon. For the modified shrinking sphere model, the reaction rate was first order with respect to CO2 but 2/3 order with respect to carbon. For simplicity, none of the models incorporated physical characteristics such as porosity or surface area. Statistical analysis showed the shrinking sphere model provided the best fit for most of gasification rates. Kinetic parameters, such as the apparent rate constant k app, and apparent activation energy Eapp, were derived from the simplified model and shrinking sphere model. The values of the apparent activation energy were comparable for the two models and to those from earlier studies.;A positive synergistic effect on the gasification reaction rate was observed between some coal char and biomass char pairs. These char pairs included: Illinois No.6 mixed with Switchgrass, Illinois No.6 mixed with Hardwood, and Powder River Basin mixed with Corn Stover. Based on Inductively Coupled Plasma -- Mass Spectrometry (ICPMS) analysis and predictive modeling of the apparent activation energy, the amount of Alkali and Alkaline Earth metals bound in the biomass chars was found to cause the positive synergistic effect and the enhanced gasification rate of the coal char

    Dual in vivo Photoacoustic and Fluorescence Imaging of HER2 Expression in Breast Tumors for Diagnosis, Margin Assessment, and Surgical Guidance

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    Biomarker-specific imaging probes offer ways to improve molecular diagnosis, intraoperative margin assessment, and tumor resection. Fluorescence and photoacoustic imaging probes are of particular interest for clinical applications because the combination enables deeper tissue penetration for tumor detection while maintaining imaging sensitivity compared to a single optical imaging modality. Here we describe the development of a human epidermal growth factor receptor 2 (HER2)-targeting imaging probe to visualize differential levels of HER2 expression in a breast cancer model. Specifically, we labeled trastuzumab with Black Hole Quencher 3 (BHQ3) and fluorescein for photoacoustic and fluorescence imaging of HER2 overexpression, respectively. The dual-labeled trastuzumab was tested for its ability to detect HER2 overexpression in vitro and in vivo. We demonstrated an over twofold increase in the signal intensity for HER2-overexpressing tumors in vivo, compared to low–HER2-expressing tumors, using photoacoustic imaging. Furthermore, we demonstrated the feasibility of detecting tumors and positive surgical margins by fluorescence imaging. These results suggest that multimodal HER2-specific imaging of breast cancer using the BHQ3-fluorescein trastuzumab enables molecular-level detection and surgical margin assessment of breast tumors in vivo. This technique may have future clinical impact for primary lesion detection, as well as intraoperative molecular-level surgical guidance in breast cancer

    Dual in vivo Photoacoustic and Fluorescence Imaging of HER2 Expression in Breast Tumors for Diagnosis, Margin Assessment, and Surgical Guidance

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    Biomarker-specific imaging probes offer ways to improve molecular diagnosis, intraoperative margin assessment, and tumor resection. Fluorescence and photoacoustic imaging probes are of particular interest for clinical applications because the combination enables deeper tissue penetration for tumor detection while maintaining imaging sensitivity compared to a single optical imaging modality. Here we describe the development of a human epidermal growth factor receptor 2 (HER2)-targeting imaging probe to visualize differential levels of HER2 expression in a breast cancer model. Specifically, we labeled trastuzumab with Black Hole Quencher 3 (BHQ3) and fluorescein for photoacoustic and fluorescence imaging of HER2 overexpression, respectively. The dual-labeled trastuzumab was tested for its ability to detect HER2 overexpression in vitro and in vivo. We demonstrated an over twofold increase in the signal intensity for HER2-overexpressing tumors in vivo, compared to low–HER2-expressing tumors, using photoacoustic imaging. Furthermore, we demonstrated the feasibility of detecting tumors and positive surgical margins by fluorescence imaging. These results suggest that multimodal HER2-specific imaging of breast cancer using the BHQ3-fluorescein trastuzumab enables molecular-level detection and surgical margin assessment of breast tumors in vivo. This technique may have future clinical impact for primary lesion detection, as well as intraoperative molecular-level surgical guidance in breast cancer

    Porphyrin-lipid stabilized paclitaxel nanoemulsion for combined photodynamic therapy and chemotherapy

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    Abstract Background Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform. Results PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core–shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning. Conclusion PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment. Graphic Abstrac

    The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death

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    Purpose: Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid near-infrared fluorescence (NIRF) imaging probe, HQ4, which was radiolabeled with "'Indium-chloride el In-C13) via the chelate diethylene triamine pentaacetic acid (DTPA), to enable clinical translation. The aim of the present study was to evaluate the application of HQ4-DTPA for monitoring tumor cell death induced by radiation therapy. Apart from its NIRF and radioactive properties, HQ4-DTPA was also tested as a photoacoustic imaging probe to evaluate its performance as a multimodal contrast agent for superficial and deep tissue imaging. Materials and methods: Radiation-induced tumor cell death was examined in a xenograft mouse model of human breast cancer (MCF-7). Tumors were irradiated with three fractions of 9 Gy each. HQ4-DTPA was injected intravenously after the last irradiation, NIRF and photoacoustic imaging of the tumors were performed at 12, 20, and 40 h after injection. Changes in probe accumulation in the tumors were measured in vivo, and ex vivo histological analysis of excised tumors was performed at experimental endpoints. In addition, biodistribution of radiolabeled [In]DTPA-HQ4 was assessed using hybrid single-photon emission computed tomography computed tomography (SPECT CT) at the same time points. Results: In vivo NIRF imaging demonstrated a significant difference in probe accumulation between control and irradiated tumors at all time points after injection. A similar trend was observed using in vivo photoacoustic imaging, which was validated by ex vivo tissue fluorescence and photoacoustic imaging. Serial quantitative radioactivity measurements of probe biodistribution further demonstrated increased probe accumulation in irradiated tumors. Conclusion: HQ4-DTPA has high specificity for dead cells in vivo, potentiating its use as a contrast agent for determining the relative level of tumor cell death following radiation therapy using NIRF, photoacoustic imaging and SPECT in vivo. Initial preclinical results are promising and indicate the need for further evaluation in larger cohorts. If successful, such studies may help develop a new multimodal method for non-invasive and dynamic deep tissue imaging of treatment-induced cell death to quantitatively assess therapeutic response in patients

    The necrosis-avid small molecule HQ4-DTPA as a multimodal imaging agent for monitoring radiation therapy-induced tumor cell death

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    textabstractPurpose: Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid near-infrared fluorescence (NIRF) imaging probe, HQ4, which was radiolabeled with 111Indium-chloride (111In-Cl3) via the chelate diethylene triamine pentaacetic acid (DTPA), to enable clinical translation. The aim of the present study was to evaluate the application of HQ4-DTPA for monitoring tumor cell death induced by radiation therapy. Apart from its NIRF and radioactive properties, HQ4-DTPA was also tested as a photoacoustic imaging probe to evaluate its performance as a multimodal contrast agent for superficial and deep tissue imaging. Materials and methods: Radiation-induced tumor cell death was examined in a xenograft mouse model of human breast cancer (MCF-7). Tumors were irradiated with three fractions of 9 Gy each. HQ4-DTPA was injected intravenously after the last irradiation, NIRF and photoacoustic imaging of the tumors were performed at 12, 20, and 40 h after injection. Changes in probe accumulation in the tumors were measured in vivo, and ex vivo histological analysis of excised tumors was performed at experimental endpoints. In addition, biodistribution of radiolabeled [111In]DTPA-HQ4 was assessed using hybrid single-photon emission computed tomography-computed tomography (SPECT-CT) at the same time points. Results: In vivo NIRF imagin

    In vivo optical imaging of tumor and microvascular response to ionizing radiation.

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    Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively--with cellular and sub-cellular details--the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo

    Longitudinal intravital fluorescence and svOCT imaging of radioresponse in tumor and vascular compartments <i>in vivo</i>.

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    <p><b>A.</b> Functional changes in perfusion in the tumor microvasculature can be seen over time (FITC-Dextran fluorescence, green) as well as tumor response (DsRed fluorescence, red) following a single fraction of 30 Gy. Image acquisition settings were kept consistent across all the time points. As early as day 4, and maximally at days 8–10 after irradiation, FITC-Dextran signal decreases significantly, indicating capillary constriction resulting in reduction in perfused blood volume. By day 10, there is disruption of blood flow in both large (∼40 µm diameters) and small (∼10 µm diameters) vessels outside and within the tumor. However, the vasculature at these time points is still intact (as seen in svOCT images of corresponding time points). <b>B.</b> At day 20 after irradiation, blood vessel perfusion resumes in most vessels around the tumor periphery (<i>white arrows</i>), while some vessels appear patent (seen intact in svOCT) without reperfusion as seen in FITC-Dextran (<i>yellow arrows</i>), and newly perfused vessels can be observed within the tumor (<i>blue arrows</i>). Corresponding svOCT images demonstrate structural changes in the vasculature, particularly close to the tumor margin and within the tumor after irradiation. This was most pronounced at days 8–10. Quantification of <b>C.</b> functional vessel density (FITC-Dextran) and <b>D.</b> mean vessel density (svOCT), normalized to day 0, of 3 ROI's in irradiated mouse over 20 days. <i>Scale bars: 400 µm (A,B).</i></p
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