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Identification and imaging of miR-155 in the early screening of lung cancer by targeted delivery of octreotide-conjugated chitosan-molecular beacon nanoparticles
摘要： Lung cancer is still the most common cancer globally. Early screening remains the key to improve the prognosis of patients. There is currently a lack of specific and sensitive methods for early screening of lung cancer. In recent years, studies have found that microRNA plays an important role in the occurrence and development of lung cancer and become a biological target in the early diagnosis of lung cancer. In this study, lung cancer cells, subcutaneous xenografts of lung cancer in nude mice, and Lox-Stop-lox K-ras G12D transgenic mice were used as models. The transgenic mice displayed the dynamic processes from normal lung tissue to atypical hyperplasia, adenomas, carcinoma in situ and lung adenocarcinoma. It was found that miR-155 and somatostatin receptor 2 (SSTR2) were expressed in all the disease stages of transgenic mice. Through molecular beacon (MB) technology and nanotechnology, chitosan-molecular beacon (CS-MB) nanoparticles and targeted octreotide (OCT) were conjugated and synthesized. The octreotide-conjugated chitosan-molecular beacon nanoparticles (CS-MB-OCT) can specifically bind to SSTR2 expressed by the lung cancer cells to achieve the goal of identification of lung cancer cells and imaging miR-155 in vivo and in vitro. Fluorescence imaging at different disease stages of lung cancer in Lox-Stop-lox K-ras G12D transgenic mice was performed, and could dynamically monitor the occurrence and development of lung cancer by different fluorescence intensity ranges. The current research, in turn, provides new idea, new method, and new technology for the early screening of lung cancer.
关键词： chitosan nanoparticles,molecular imaging,molecular beacon,Lung cancer,microRNA-155
更新于2025-09-23 15:23:52
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A promising family of fluorescent water-soluble aza-BODIPY dyes for in vivo molecular imaging
摘要： A new family of water-soluble and bioconjugatable aza-BODIPY fluorophores was designed and synthesized using a boron-functionalization strategy. These dissymmetric bis-ammonium aza-BODIPY dyes present optimal properties for a fluorescent probe, i.e. they are highly water-soluble, very stable in physiological medium, they do not aggregate in PBS, possess high quantum yield and finally they can be easily bioconjugated to antibodies. Preliminary in vitro and in vivo studies were performed for one of these fluorophores to image PD-L1 (Programmed Death-Ligand 1), highlighting the high potential of these new probes for future in vivo optical imaging studies.
关键词： molecular Imaging,Fluorescent probes,boron functionalization,aza-BODIPY,Water-soluble fluorophores
更新于2025-09-23 15:23:52
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Paired-Agent Fluorescence Molecular Imaging of Sentinel Lymph Nodes Using Indocyanine Green as a Control Agent for Antibody-Based Targeted Agents
摘要： Purpose. Paired-agent molecular imaging methods, which employ coadministration of an untargeted, “control” imaging agent with a targeted agent to correct for nonspecific uptake, have been demonstrated to detect 200 cancer cells in a mouse model of metastatic breast cancer. This study demonstrates that indocyanine green (ICG), which is approved for human use, is an ideal control agent for future paired-agent studies to facilitate eventual clinical translation. Methods. The kinetics of ICG were compared with a known ideal control imaging agent, IRDye-700DX-labeled antibody in both healthy and metastatic rat popliteal lymph nodes after coadministration, intradermally in the footpad. Results. The kinetics of ICG and antibody-based imaging agent in tumor-free rat lymph nodes demonstrated a strong correlation with each other (r = 0.98, p < 0.001) with a measured binding potential of -0.102 ± 0.03 at 20 min postagent injection, while the kinetics of ICG and targeted imaging agent shows significant separation in the metastatic lymph nodes. Conclusion. This study indicated a potential for microscopic sensitivity to cancer spread in sentinel lymph nodes using ICG as a control agent for antibody-based molecular imaging assays.
关键词： Paired-agent imaging,Antibody-based targeted agents,Control agent,Indocyanine green,Fluorescence molecular imaging,Sentinel lymph node
更新于2025-09-23 15:22:29
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In vivo long-term investigation of tumor bearing mKate2 by an in-house fluorescence molecular imaging system
摘要： Background: Optical imaging is one of the most common, low-cost imaging tools used for investigating the tumor biological behavior in vivo. This study explores the feasibility and sensitivity of a near infrared fluorescent protein mKate2 for a long-term non-invasive tumor imaging in BALB/c nude mice, by using a low-power optical imaging system. Methods: In this study, breast cancer cell line MDA-MB-435s expressing mKate2 and MDA-MB-231 expressing a dual reporter gene firefly luciferase (fLuc)-GFP were used as cell models. Tumor cells were implanted in different animal body compartments including subcutaneous, abdominal and deep tissue area and closely monitored in real-time. A simple and low-power optical imaging system was set up to image both fluorescence and bioluminescence in live animals. Results: The presence of malignant tissue was further confirmed by histopathological assay. Considering its lower exposure time and no need of substrate injection, mKate2 is considered a superior choice for subcutaneous imaging compared with fLuc. On the contrary, fLuc has shown to be a better option when monitoring the tumor in a diffusive area such as abdominal cavity. Furthermore, both reporter genes have shown good stability and sensitivity for deep tissue imaging, i.e. tumor within the liver. In addition, fLuc has shown to be an excellent method for detecting tumor cells in the lung. Conclusions: The combination of mKate2 and fLuc offers a superior choice for long-term non-invasive real-time investigation of tumor biological behavior in vivo.
关键词： Molecular imaging,mKate2,Luciferase,Tumor cell tagging
更新于2025-09-23 15:22:29
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99mTc sestamibi SPECT: a possible tool for early detection of breast cancer lesions with high bone metastatic potential
摘要： The early identification of lesions with high metastatic potential by 99mTc sestamibi high-resolution SPECT analysis could be considered a new frontier for diagnosis and/or therapy of breast lesions.
关键词： SPECT,breast cancer,molecular imaging,breast osteoblast-like cells,99mTc sestamibi
更新于2025-09-23 15:22:29
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Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody
摘要： Inadequate diagnostic methods for prostate cancer lead to over- and undertreatment, and the inability to intraoperatively visualize positive margins may limit the success of surgical resection. Prostate cancer visualization could be improved by combining the complementary modalities of immuno-positron emission tomography (immunoPET) for preoperative disease detection, and fluorescence imaging-guided surgery (FIGS) for real-time intraoperative tumor margin identification. Here, we report on the evaluation of dual-labeled humanized anti-prostate stem cell antigen (PSCA) cys-minibody (A11 cMb) for immunoPET/fluorescence imaging in subcutaneous and orthotopic prostate cancer models. Methods: A11 cMb was site-specifically conjugated with the near-infrared fluorophore Cy5.5 and radiolabeled with 124I or 89Zr. 124I-A11 cMb-Cy5.5 was used for successive immunoPET/fluorescence imaging of prostate cancer xenografts expressing high or moderate levels of PSCA (22Rv1-PSCA and PC3-PSCA). 89Zr-A11 cMb-Cy5.5 dual-modality imaging was evaluated in an orthotopic model. Ex vivo biodistribution at 24 h was used to confirm the uptake values, and tumors were visualized by post-mortem fluorescence imaging. Results: A11 cMb-Cy5.5 retained low nanomolar affinity for PSCA-positive cells. Conjugation conditions were established (dye-to-protein ratio of 0.7:1) that did not affect the biodistribution, pharmacokinetics, or clearance of A11 cMb. ImmunoPET using dual-labeled 124I-A11 cMb-Cy5.5 showed specific targeting to both 22Rv1-PSCA and PC3-PSCA s.c. xenografts in nude mice. Ex vivo biodistribution confirmed specific uptake to PSCA-expressing tumors with 22Rv1-PSCA:22Rv1 and PC3-PSCA:PC3 ratios of 13:1 and 5.6:1, respectively. Consistent with the immunoPET, fluorescence imaging showed a strong signal from both 22Rv1-PSCA and PC3-PSCA tumors compared with non-PSCA expressing tumors. In an orthotopic model, 89Zr-A11 cMb-Cy5.5 immunoPET was able to detect intraprostatically implanted 22Rv1-PSCA cells. Importantly, fluorescence imaging clearly distinguished the prostate tumor from surrounding seminal vesicles. Conclusion: Dual-labeled A11 cMb specifically visualized PSCA-positive tumor by successive immunoPET/fluorescence, which can potentially be translated for preoperative whole-body prostate cancer detection and intraoperative surgical guidance in patients.
关键词： molecular imaging,immunoPET,prostate cancer,antibody fragment,fluorescence
更新于2025-09-23 15:22:29
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Dual-modality optical projection tomography reconstruction method from fewer views
摘要： In optical projection tomography (OPT), for longitudinal living model studies, multiple measurements of the same sample are required at different time points. It is important to decrease both the total acquisition time and the light dose to the sample. We improved the ordered subsets expectation maximization reconstruction algorithm for OPT, which reduces the acquisition time and number of projections greatly compared with filtered back projection (FBP), and satisfactory reconstructed images are obtained. Using zebrafish, in transmission and fluorescence mode, we demonstrate the capability of the method to reconstruct image from downsampled projection subsets. The result shows that the reconstruction image quality of the proposed method using 30 projections is comparable to that of FBP using 720 projections. The total acquisition procedure can be finished in a few seconds. The method also provides OPT with the remarkable capability to resist noises and artifacts.
关键词： molecular imaging,image reconstruction,dual-modality OPT,preimaging calibration
更新于2025-09-23 15:22:29
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<sup>18</sup> F-Fluoride Signal Amplification Identifies Microcalcifications Associated With Atherosclerotic Plaque Instability in Positron Emission Tomography/Computed Tomography Images
摘要： BACKGROUND: Microcalcifications in atherosclerotic plaques are destabilizing, predict adverse cardiovascular events, and are associated with increased morbidity and mortality. 18F-fluoride positron emission tomography (PET)/computed tomography (CT) imaging has demonstrated promise as a useful clinical diagnostic tool in identifying high-risk plaques; however, there is confusion as to the underlying mechanism of signal amplification seen in PET-positive, CT-negative image regions. This study tested the hypothesis that 18F-fluoride PET/CT can identify early microcalcifications. METHODS: 18F-fluoride signal amplification derived from microcalcifications was validated against near-infrared fluorescence molecular imaging and histology using an in vitro 3-dimensional hydrogel collagen platform, ex vivo human specimens, and a mouse model of atherosclerosis. RESULTS: Microcalcification size correlated inversely with collagen concentration. The 18F-fluoride ligand bound to microcalcifications formed by calcifying vascular smooth muscle cell derived extracellular vesicles in the in vitro 3-dimensional collagen system and exhibited an increasing signal with an increase in collagen concentration (0.25 mg/mL collagen ?33.8×102±12.4×102 counts per minute; 0.5 mg/mL collagen ?67.7×102±37.4×102 counts per minute; P=0.0014), suggesting amplification of the PET signal by smaller microcalcifications. We further incubated human atherosclerotic endarterectomy specimens with clinically relevant concentrations of 18F-fluoride. The 18F-fluoride ligand labeled microcalcifications in PET-positive, CT-negative regions of explanted human specimens as evidenced by 18F-fluoride PET/CT imaging, near-infrared fluorescence, and histological analysis. Additionally, the 18F-fluoride ligand identified micro and macrocalcifications in atherosclerotic aortas obtained from low-density lipoprotein receptor-deficient mice. CONCLUSIONS: Our results suggest that 18F-fluoride PET signal in PET-positive, CT-negative regions of human atherosclerotic plaques is the result of developing microcalcifications, and high surface area in regions of small microcalcifications may amplify PET signal.
关键词： molecular imaging,fluoride,atherosclerosis,positron emission tomography,microcalcification
更新于2025-09-23 15:22:29
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Live-cell super-resolution microscopy reveals a primary role for diffusion in polyglutamine-driven aggresome assembly
摘要： The mechanisms leading to self-assembly of misfolded proteins into amyloid aggregates have been studied extensively in the test tube under well-controlled conditions. However, to what extent these processes are representative of those in the cellular environment remains unclear. Using super-resolution imaging of live cells, we show here that an amyloidogenic polyglutamine-containing protein first forms small, amorphous aggregate clusters in the cytosol, chiefly by diffusion. Dynamic interactions among these clusters limited their elongation and led to structures with a branched morphology, differing from the predominantly linear fibrils observed in vitro. Some of these clusters then assembled via active transport at the microtubule-organizing center and thereby initiated the formation of perinuclear aggresomes. Although it is widely believed that aggresome formation is entirely governed by active transport along microtubules, here we demonstrate, using a combined approach of advanced imaging and mathematical modeling, that diffusion is the principal mechanism driving aggresome expansion. We found that increasing surface area of the expanding aggresome increases the rate of accretion due to diffusion of cytosolic aggregates and that this pathway soon dominates aggresome assembly. Our findings lead to a different view of aggresome formation than that proposed previously. We also show that aggresomes mature over time, becoming more compacted as the structure grows. The presence of large perinuclear aggregates profoundly affects the behavior and health of the cell, and our super-resolution imaging results indicate that aggresome formation and development are governed by highly dynamic processes that could be important for the design of potential therapeutic strategies.
关键词： molecular modelling,protein aggregation,molecular imaging,passive transport,amyloid protein,aggresome formation,transport,live cell SIM,protein misfolding,molecular dynamics
更新于2025-09-23 15:21:21
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Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals
摘要： Antibodies and their derivatives radiolabelled with positron- and gamma-emitting radiometals enable sensitive and quantitative molecular Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging of antibody distribution in vivo. Chelators that are covalently attached to antibodies allow radiolabelling with metallic PET and SPECT radioisotopes. Conventional strategies for chelator-protein conjugation generate heterogeneous mixtures of bioconjugates that can exhibit reduced affinity for their targets, and undesirable biodistribution and pharmacokinetics. Recent advances in bioconjugation technology enable site-specific modification to generate well-defined constructs with superior properties. Herein we survey existing site-specific chelator-protein conjugation methods. These include chelator attachment to cysteines/disulfide bonds or the glycan region of the antibody, enzyme-mediated chelator conjugation, and incorporation of sequences of amino acids that chelate the radiometal. Such technology will allow better use of PET and SPECT imaging in the development of antibody-based therapies.
关键词： antibody,radiometals,PET,chelator,site-specific conjugation,SPECT,molecular imaging
更新于2025-09-23 15:21:21