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Showing papers by "Xiaoyuan Chen published in 2011"


Journal ArticleDOI
TL;DR: The surface engineering techniques that the authors and others have developed are introduced, with an emphasis on how these techniques affect the role of nanoparticles as imaging or therapeutic agents.
Abstract: Enormous efforts have been made toward the translation of nanotechnology into medical practice, including cancer management. Generally the applications have fallen into two categories: diagnosis and therapy. Because the targets are often the same, the development of separate approaches can miss opportunities to improve efficiency and effectiveness.The unique physical properties of nanomaterials enable them to serve as the basis for superior imaging probes to locate and report cancerous lesions and as vehicles to deliver therapeutics preferentially to those lesions. These technologies for probes and vehicles have converged in the current efforts to develop nanotheranostics, nanoplatforms with both imaging and therapeutic functionalities. These new multimodal platforms are highly versatile and valuable components of the emerging trend toward personalized medicine, which emphasizes tailoring treatments to the biology of individual patients to optimize outcomes. The close coupling of imaging and treatment wit...

517 citations


Journal ArticleDOI
TL;DR: In vivo antitumor tests revealed that CCM-HSA-NPs had a greater therapeutic effect than CCM (50% or 66% tumor growth inhibition vs. PBS-treated controls) in tumor xenograft HCT116 models without inducing toxicity.

259 citations


Journal ArticleDOI
TL;DR: A good tumor targeting profile was observed, which was attributable to both the enhanced permeability and retention (EPR) effect and biovector mediated targeting, which promises ferritin particles as a powerful nanoplatfom in the era of nanomedicine.
Abstract: Nanomaterials provide large surface areas, relativeto their volumes, on which to load functions. One challenge, however, has been to achieve precise control in loading multiple functionalities. Traditional bioconjugation techniques, which randomly target the surface functional groups of nanomaterials, have been found increasingly inadequate for such control, which is a drawback that may substantially slow down or prohibit the translational efforts. In the current study, we evaluated ferritin nanocages as candidate nanoplatforms for multifunctional loading. Ferritin nanocages can be either genetically or chemically modified to impart functionalities to their surfaces, and metal cations can be encapsulated in their interiors by association with metal binding sites. Moreover, different types of ferritin nanocages can be disassembled under acidic condition and reassembled at pH of 7.4, providing a facile way to achieve function hybridization. We were able to use combinations of these unique properties to prod...

231 citations


Journal ArticleDOI
TL;DR: This review explores the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explores current uses of activatable probes, and proposes an engineering approach for future development of fluorescence based gold nanoparticles activatable probe probes.
Abstract: Fluorescence-based assays and detection techniques are among the most highly sensitive and popular biological tests for researchers. To match the needs of research and the clinic, detection limits and specificities need to improve, however. One mechanism is to decrease non-specific background signals, which is most efficiently done by increasing fluorescence quenching abilities. Reports in the literature of theoretical and experimental work have shown that metallic gold surfaces and nanoparticles are ultra-efficient fluorescence quenchers. Based on these findings, subsequent reports have described gold nanoparticle fluorescence-based activatable probes that were designed to increase fluorescence intensity based on a range of stimuli. In this way, these probes can detect and signify assorted biomarkers and changes in environmental conditions. In this review, we explore the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explore current uses of activatable probes, and propose an engineering approach for future development of fluorescence based gold nanoparticle activatable probes.

211 citations


Journal ArticleDOI
TL;DR: Integrin αvβ3 is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial Cells and most normal organ systems, making it a suitable target for anti-tumor therapy.
Abstract: Targeted delivery of chemotherapeutics is defined in the sense, that is, to maximize the therapeutic index of a chemotherapeutic agent by strictly localizing its pharmacological activity to the site or tissue of action. Integrins are a family of heterodimeric transmembrane glycoproteins involved in a wide range of cell-to-extracellular matrix (ECM) and cell-to-cell interactions. As cell surface receptors, integrins readily interact with extracellular ligands and play a vital role in angiogenesis, leukocytes function and tumor development, which sets up integrins as an excellent target for chemotherapy treatment. The peptide ligands containing the arginine-glycine-aspartic acid (RGD), which displays a strong binding affinity and selectivity to integrins, particularly to integrin αvβ3, have been developed to conjugate with various conventional chemotherapeutic agents, such as small molecules, peptides and proteins, and nanoparticle-carried drugs for integtrin targeted therapeutic studies. This review highlights the recent advances in integrin targeted delivery of chemotherapeutic agents with emphasis on target of integrin αvβ3, and describes the considerations for the design of the diverse RGD peptide-chemotherapeutics conjugates and their major applications.

203 citations


Journal ArticleDOI
TL;DR: D-HINPs showed a striking tumor suppression effect that was comparable to that of Doxil and greatly outperformed free Dox and can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform.
Abstract: An ongoing effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the "nanotheranostics". We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting D-HINPs (Dox loaded HINPs) have a hydrodynamic size of 50 nm and are able to release Dox in a sustained fashion. More impressively, the HINPs can assist the translocation of Dox across the cell membrane and even its accumulation in the nucleus. In vivo, D-HINPs retained a tumor targeting capability of HINPs, as manifested by both in vivo MRI and ex vivo immunostaining results. In a follow-up therapeutic study on a 4T1 murine breast cancer xenograft model, D-HINPs showed a striking tumor suppression effect that was comparable to that of Doxil and greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform.

199 citations


Journal ArticleDOI
TL;DR: This review attempts to give a summary of progress in using nanotechnology to monitor cell trafficking by focusing on direct cell labeling techniques, in which cells ingest nanoparticles that bear traceable signals, such as iron oxide or quantum dots.
Abstract: Cell based therapeutics are emerging as powerful regimens. To better understand the migration and proliferation mechanisms of implanted cells, a means to track cells in living subjects is essential, and to achieve that, a number of cell labeling techniques have been developed. Nanoparticles, with their superior physical properties, have become the materials of choice in many investigations along this line. Owing to inherent magnetic, optical or acoustic attributes, these nanoparticles can be detected by corresponding imaging modalities in living subjects at a high spatial and temporal resolution. These features allow implanted cells to be separated from host cells; and have advantages over traditional histological methods, as they permit non-invasive, real-time tracking in vivo. This review attempts to give a summary of progress in using nanotechnology to monitor cell trafficking. We will focus on direct cell labeling techniques, in which cells ingest nanoparticles that bear traceable signals, such as iron oxide or quantum dots. Ferritin and MagA reporter genes that can package endogenous iron or iron supplement into iron oxide nanoparticles will also be discussed.

186 citations


Journal ArticleDOI
TL;DR: Results proved that this tumor-homing cellular 'on/off' nanoparticle system of PpIX-GC-NPs has a great potential for synchronous photodynamic imaging and therapy in cancer treatment.

158 citations


Journal ArticleDOI
TL;DR: A novel method to detect enzymatic activity at the single particle level inside and outside cells by DFM is described, which is the first time to monitor the intracellular metabolism and the effect of anticancer drugs on the cell metabolism using copper growth on the AuNP probes.
Abstract: Plasmonics, is an emerging subfield of nanophontonics, and it attracts increasing attention because of its potential applications in controlling and manipulating light at nanoscale dimensions. The advent of dark-field microscopy (DFM) has enabled the study of plasmonic nanoparticles, especially the coinage metals and the effects of their size, shape, composition as well as the local environment, which further facilitate its use in biological-labeling and detection. DFM provides a direct means to probe chemical reactions, real-time optical sensing with high sensitivity, and the in vivo imaging of cancer cells. Recently, redox reactions were directly monitored on single gold nanocrystals using DFM. Actually, every individual nanoparticle (NP) in the assembly could potentially act as an independent probe. Single-nanoparticle sensing platforms offer advantages since they are readily implemented in multiplex detection. Single nanoparticle probes offer improved absolute detection limits and also enable higher spatial resolution. Single nanoparticles have promising applications for measurements in vitro and in vivo events that are non-reachable by fixed solid array. However, the use of plasmonic nanoparticles for the detection of biomolecules or biological processes is still scarce. Nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) plays an important role as cofactor in numerous biocatalyzed processes, including energy metabolism, mitochondrial responses, immunological functions, aging and cell death. The catalytic deposition of copper on gold nanoparticles (AuNPs) by the NADH cofactor has been applied for the optical and electrochemical detection of NADH and NAD-dependent biocatalytic processes. Herein, we describe a novel method to detect enzymatic activity at the single particle level inside and outside cells by DFM. To our knowledge, it is the first time to monitor the intracellular metabolism and the effect of anticancer drugs on the cell metabolism using copper growth on the AuNP probes. To investigate the application of single Au@Cu nanoparticles for nano-sensing, the plasmon resonance Rayleigh scattering (PRRS) spectra lmax of a single particle was used to probe the gold-catalyzed reduction of Cu ions on AuNPs by NADH or by NAD-cofactor-dependent enzyme/substrate system that generates NADH (Scheme 1). Compared with the scattering spectra in the absence of NADH, the scattering spectra acquired with NADH exhibit a distinct peak shift

153 citations


Journal ArticleDOI
TL;DR: Considering their ease of preparation and good imaging qualities, [(18)F]FAl-NOTA-PRGD2 and [(68)Ga]-labeled NOTA-RGD derivatives are promising alternatives to [(18]F]FPPR GD2 for PET imaging of tumor α(v)β(3) integrin expression.

140 citations


Journal ArticleDOI
TL;DR: An efficient SPIO probe has been developed for mesenchymal stem cells labeling and tracking at optimized low dosages with high efficiency, and the probe may be useful to label other biologically important cells for imaging studies.

Journal ArticleDOI
TL;DR: In vitro and in vivo study showed the affibody-based nanoprobes specifically target and image human epidermal growth factor receptor type 2 (HER2)-expressing cells and tumors.

Journal ArticleDOI
TL;DR: The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values, and tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values were evaluated.
Abstract: The radiopharmaceutical agent 18F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties, with the latter favoring PET applications in the head, neck, thorax, and extremities.

Journal ArticleDOI
TL;DR: This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation and special emphasis was placed on noninvasive imaging hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to tumor Hypoxia.
Abstract: There is a need to measure tumor hypoxia in assessing the aggressiveness of tumor and predicting the outcome of therapy. A number of invasive and noninvasive techniques have been exploited to measure tumor hypoxia, including polarographic needle electrodes, immunohistochemical staining, radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), magnetic resonance imaging (MRI), optical imaging (bioluminescence and fluorescence), and so on. This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation. Special emphasis was placed on noninvasive imaging hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to tumor hypoxia.

Journal ArticleDOI
04 Oct 2011-Small
TL;DR: A nonviral nanoparticle gene carrier developed and its efficiency for siRNA delivery and transfection is validated at both in vitro and in vivo levels, demonstrating highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy.
Abstract: Small-interfering RNA (siRNA) is an emerging class of therapeutics, which works by regulating the expression of a specific gene involved in disease progression. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. In this study, a nonviral nanoparticle gene carrier is developed and its efficiency for siRNA delivery and transfection is validated at both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k-IO, was constructed with a core of iron oxide nanoparticles (IOs) and a shell of alkylated polyethyleneimine of 2000 Da [corrected] molecualr weight (Alkyl-PEI2k). It is found to be able to bind with siRNA, resulting in well-dispersed nanoparticles with a controlled clustering structure and narrow size distribution. Electrophoresis studies show that the Alkyl-PEI2k-IOs could retard siRNA completely at N:P ratios (i.e., PEI nitrogen to nucleic acid phosphate) above 10, protect siRNA from enzymatic degradation in serum, and release complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown efficiency of the siRNA-loaded nanocarriers is assessed with 4T1 cells stably expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model. Significant down-regulation of luciferase is observed, and unlike high-molecular-weight analogues, the Alkyl-PEI2k-coated IOs show good biocompatibility. In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy.

Journal ArticleDOI
TL;DR: An overview of the current status and trends in the development of non-[(18)F]FDG PET probes in oncology and their application in the investigation of cancer biology is provided.

Journal ArticleDOI
TL;DR: Activatable probes are developed, designed to be fluorescently quenched at a quiescent stage but activatable when encountering a specific trigger, which leads to a structural or conformational change and restores fluorescence activities.
Abstract: Near-infrared fluorescence (NIRF) imaging is emerging as an important tool in preclinical studies.[1–5] As the technology is being established and implemented worldwide, a wave of effort has been spurred to develop novel imaging probes that can accurately recognize and report diseases, such as cancer.[3,6] One common drawback of NIRF imaging, however, is its high background and as a consequence of that, low specificity.[7,8] To address this issue, we and others have developed activatable probes with various approaches. Such probes, constructed by bringing into proximity an energy donor and receptor, are designed to be fluorescently quenched at a quiescent stage but activatable when encountering a specific trigger, which leads to a structural or conformational change and restores fluorescence activities.[7–9] This technique allows the signals to be only amplified at diseased areas upon a designated environment change, a feature which can greatly improve the signal-to-background ratio.

Journal ArticleDOI
26 Apr 2011-ACS Nano
TL;DR: This work has used a flower-shaped Au-Fe3O4 nanoparticle as a template to construct an optical probe that can be specifically activated by matrix metalloproteinases expressed in tumors.
Abstract: We and others have recently proposed the synthesis of composite nanoparticles that offer strongly enhanced functionality. Here we have used a flower-shaped Au-Fe3O4 nanoparticle as a template to construct an optical probe containing Cy5.5-GPLGVRG-TDOPA on the iron oxide surface and SH-PEG5000 on the gold surface that can be specifically activated by matrix metalloproteinases (MMPs) expressed in tumors. Gold nanoparticles have excellent quenching properties, but labile surface chemistry in vivo; on the other hand, iron oxide nanoparticles afford robust surface chemistry, but are suboptimal as energy receptors. By a marriage of the two, we have produced a unified structure with performance that is unachievable with the separate components. Our results are a further demonstration that the architecture of nanoparticles can be modulated to tailor their function as molecular imaging/therapeutic agents.

Journal ArticleDOI
TL;DR: The current methods for evaluating response to treatment are examined and an overview of emerging PET molecular imaging methods that will help guide future cancer therapies are provided.
Abstract: The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies.

Journal ArticleDOI
TL;DR: In this review, the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles are discussed.
Abstract: Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle–based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles. I NORGANIC NANOPARTICLES offer many unique advantages for multimodal imaging owing to their unique size- and shape-dependent physical and chemical properties. Inorganic nanoparticles such as magnetic iron oxide nanoparticles (IONPs) are studied as magnetic resonance imaging (MRI) contrast agents, 1 semiconducting quantum dots (QDs) serve as optical probes for intracellular organelles and biomolecules, 2 metallic gold nanoparticles (AuNPs) exhibit unique light scattering patterns for surface-enhanced Raman spectroscopy, 3 and other particles exhibit unique properties useful for molecular imaging. The development of inorganic nanoparticles has grown tremendously owing to advances in synthesis methods and combination with other organic substances. 4 For the last 5 years, the number of publications for ‘‘inorganic nanoparticles’’ on the ISI Web of Knowledge database has increased steadily, totaling a 150% increase. This steady increase is mainly due to the discovery that these nanomaterials offer a unique high aspect ratio platform for multifunctionality, where multiple ligands such as targeting agents, drugs, and radioisotopes can be attached onto one particle for the possibility of molecular targeting, therapeutic delivery, and multimodal imaging. 5 Nanoparticles attached with targeting ligands can enter the cell and pursue specific biomolecules, giving it true molecular imaging capabilities. 6,7 As opposed to adjusting properties in bulk materials, nanoparticle shape and size are easily fine-tuned by the advances in lithography 8,9 and wet-chemistry 10,11 techniques offering tunable magnetic and optical properties for molecular imaging. The different components of the multifunctional nanomaterials can be synthesized in a heterogeneous manner, collectively encapsulated within a nanomaterial, or added onto a singular nanoplatform. Certain nanoparticle synthesis techniques require surface encasing materials to stabilize the nanoparticles and allow for dispersion. 12 The surface coatings can be modified with additional functional groups and multiple imaging agents for multimodal molecular imaging capabilities.

Journal ArticleDOI
TL;DR: 18F-labeled BBN peptide agonists may be the probes of choice for prostate cancer imaging due to their relatively high tumor uptake and retention as compared with the antagonist counterparts.
Abstract: Radiolabeled bombesin analogs are promising probes for cancer imaging of gastrin-releasing peptide receptor (GRPR). In this study, we developed (18)F-labeled GRPR agonists and antagonists for positron emission tomography (PET) imaging of prostate cancer. GRPR antagonists ATBBN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH(2)CH(3)) and MATBBN (Gly-Gly-Gly-Arg-Asp-Asn-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH(2)CH(3)), and agonists AGBBN (Gln-Trp-Ala-Val-Gly-His-Leu-MetNH(2)) and MAGBBN (Gly-Gly-Gly-Arg-Asp-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-MetNH(2)) were radiolabeled with (18)F via 4-nitrophenyl 2-(18)F-fluoropropionate. The in vitro receptor binding, cell uptake, and efflux properties of the radiotracers were studied on PC-3 cells. An in vivo PET study was performed on mice bearing PC-3 tumors. Direct (18)F-labeling of known GRPR antagonist ATBBN and agonist AGBBN did not result in good tumor targeting or appropriate pharmacokinetics. Modification was made by introducing a highly hydrophilic linker Gly-Gly-Gly-Arg-Asp-Asn. Higher receptor binding affinity, much higher cell uptake and slower washout were observed for the agonist (18)F-FP-MAGBBN over the antagonist (18)F-FP-MATBBN. Both tracers showed good tumor/background contrast, with the agonist (18)F-FP-MAGBBN having significantly higher tumor uptake than the antagonist (18)F-FP-MATBBN (P < 0.01). In conclusion, Gly-Gly-Gly-Arg-Asp-Asn linker significantly improved the pharmacokinetics of the otherwise hydrophobic BBN radiotracers. (18)F-labeled BBN peptide agonists may be the probes of choice for prostate cancer imaging due to their relatively high tumor uptake and retention as compared with the antagonist counterparts.

Journal ArticleDOI
TL;DR: This paper demonstrates the first true real-time in vivo video imaging of extracellular protease expression using an ultrafast-acting and extended-use activatable probe and video imaged the expression and inhibition of matrix metalloproteinases in a tumor-bearing mouse model.
Abstract: We demonstrate the first true real-time in vivo video imaging of extracellular protease expression using an ultrafast-acting and extended-use activatable probe. This simple, one-step technique is capable of boosting fluorescent signals upon target protease cleavage as early as 30 minutes from injection in a small animal model and is able to sustain the strong fluorescent signal up to 24 hours. Using this method, we video imaged the expression and inhibition of matrix metalloproteinases (MMPs) in a tumor-bearing mouse model. The current platform can be universally applied to any target protease of interest with a known peptide substrate and is adaptable to a wide range of real-time imaging applications with high throughputs such as for in vivo drug screening, examinations of the therapeutic efficacy of drugs, and monitoring of disease onset and development in animal models.

Journal ArticleDOI
TL;DR: The TRAIL-PEG-NP formulation efficiently suppressed tumor growth, and histological findings confirmed that NPs induced significant tumor cell apoptosis without inducing liver toxicity.

Journal ArticleDOI
TL;DR: A derivative of the CXCR4 peptide antagonist, T140-2D, is developed that can be labeled easily with the PET isotope copper-64, and thereby enable in vivo visualization of CX CR4 in tumors, and had high uptake, however, in metabolic organs.
Abstract: Expression of CXCR4 in cancer has been found to correlate with poor prognosis and resistance to chemotherapy. In this study we developed a derivative of the CXCR4 peptide antagonist, T140-2D, that can be labeled easily with the PET isotope copper-64, and thereby enable in vivo visualization of CXCR4 in tumors. T140 was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxysuccinimide ester) (DOTA-NHS) to give T140-2D, which contains a DOTA molecule on each of the two lysine residues. (64)Cu-T140-2D was evaluated in vitro by migration and binding experiments, and in vivo by microPET imaging and biodistribution, in mice bearing CXCR4-positive and CXCR4-negative tumor xenografts. T140-2D was labeled with copper-64 to give (64)Cu-T140-2D in a high radiochemical yield of 86 ± 3% (not decay-corrected) and a specific activity of 0.28 - 0.30 mCi/µg (10.36 - 11.1 MBq/µg). (64)Cu-T140-2D had antagonistic and binding characteristics to CXCR4 that were similar to those of T140. In vivo, (64)Cu-T140-2D tended to bind to red blood cells and had to be used in a low specific activity form. In this new form (64)Cu-T140-2D enabled specific imaging of CXCR4-positive, but not CXCR4-negative tumors. Undesirably, however, (64)Cu-T140-2D also displayed high accumulation in the liver and kidneys. In conclusion, (64)Cu-T140-2D was easily labeled and, in its low activity form, enabled imaging of CXCR4 in tumors. It had high uptake, however, in metabolic organs. Further research with imaging tracers targeting CXCR4 is required.

Journal ArticleDOI
TL;DR: High tracer uptake in INS-1 tumors and receptor specificity in bothINS-1 tumor and pancreas are confirmed and the favorable characteristics of (18)F-FBEM-EM3106B, such as high specific activity and high tumor uptake, and high tumors to nontarget uptake, demonstrate that it is a promising tracer for clinical insulinoma imaging.
Abstract: Derived from endocrine pancreatic beta cells, insulinomas express glucagon-like peptide-1 (GLP-1) receptor with high density and incidence. In this study, we labeled a novel GLP-1 analogue, EM3106B, with 18F and performed PET imaging to visualize insulinoma tumors in an animal model. A GLP-1 analogue that contains multiple lactam bridges, EM3106B, was labeled with 18F through a maleimide-based prosthetic group, N-2-(4-18F-fluorobenzamido)ethylmaleimide (18F-FBEM). The newly developed radiotracer was characterized by cell based receptor-binding assay, cell uptake and efflux assay. The stability in serum was evaluated by radio-HPLC analysis. In vivo PET imaging was performed in nude mice bearing subcutaneous INS-1 insulinoma tumors and MDA-MB-435 tumors of melanoma origin. Ex vivo biodistribution study was performed to confirm the PET imaging data. EM3106B showed high binding affinity (IC50 = 1.38 nM) and high cell uptake (5.25 ± 0.61% after 120 min incubation). 18F-FBEM conjugation of EM3106B resulted in h...

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TL;DR: MT1-AF7p is an important tool for noninvasive monitoring of MT1-MMP expression in tumors, and it shows great potential as an imaging agent for MT1 -MMP-positive tumors.

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TL;DR: In this review, a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, and lymphatic nodes are provided, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic Imaging using lymphatic biomarkers, photoacoustic imaging, and combinations of multiple modalities.
Abstract: Noninvasive in vivo imaging of lymphatic vessels and lymphatic nodes is expected to fulfill the purpose of analyzing lymphatic vessels and their function, understanding molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors, and utilizing lymphatic molecular markers as a prognostic or diagnostic indicator. In this review, we provide a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, and lymphatic nodes, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic imaging such as optical imaging, computed tomography, magnetic resonance imaging, ultrasound, positron emission tomography using lymphatic biomarkers, photoacoustic imaging, and combinations of multiple modalities. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve the research of lymphatic vascular system in health and disease states as well as to improve the accuracy of diagnosis in the relevant diseases.

Journal ArticleDOI
TL;DR: A novel one-step ¹⁸F radiolabeling strategy for peptides that contain a specific arene group is developed, which shortens reaction time and labor significantly, requires low amount of precursor, and results in specific activity of 79 ± 13 GBq/μmol.

Journal ArticleDOI
TL;DR: 18F-FPPRGD2 PET is superior to 18F-FDG PET in monitoring early response to treatment, favoring its potential clinical translation and Abraxane-mediated downregulation of integrin αvβ3 expression on tumor endothelial cells can be quantitatively visualized by PET.
Abstract: Abraxane (nanoparticle albumin-bound paclitaxel) is an anticancer drug approved by the Food and Drug Administration. However, the mechanism of action of Abraxane is complex, and no established biomarker is available to accurately monitor its treatment outcomes. The aim of this study was to investigate whether the integrin-specific PET tracer 18F-FPPRGD2 (investigational new drug 104150) can be used to monitor early response of tumors to Abraxane therapy. Methods: Orthotopic MDA-MB-435 breast cancer mice were treated with Abraxane (25 mg/kg every other day, 3 doses) or phosphate-buffered saline. Tumor volume was monitored by caliper measurement. PET scans were obtained before and at different times after the start of treatment (days 0, 3, 7, 14, and 21) using 18F-FPPRGD2 and 18F-FDG. The tumoricidal effect was also assessed ex vivo by immunohistochemistry. Results: Abraxane treatment inhibited the tumor growth, and a significant difference in tumor volume could be seen at day 5 after the initiation of treatment. The tumor uptake of 18F-FPPRGD2 in the Abraxane-treated group was significantly lower on days 3 and 7 than at baseline but returned to the baseline level at days 14 and 21, indicative of relapse of the tumors after the treatment was halted. Immunohistologic staining confirmed that the change of 18F-FPPRGD2 uptake correlated with the variation of integrin level in the tumor vasculature induced by Abraxane treatment. No significant change of tumor (rather than vascular) integrin expression was observed throughout the study. No significant decrease of 18F-FDG uptake was found between the treated and the control tumors on days 3, 14, and 21, although an increase in 18F-FDG tumor uptake of treated mice, as compared with the control mice, was found on day 7. The increase of 18F-FDG on day 7 was related to the inflammatory response during therapy. Conclusion: Abraxane-mediated downregulation of integrin αvβ3 expression on tumor endothelial cells can be quantitatively visualized by PET. The change of integrin expression precedes that of tumor size. Consequently, 18F-FPPRGD2 PET is superior to 18F-FDG PET in monitoring early response to treatment, favoring its potential clinical translation.

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TL;DR: The findings suggest that TRAIL derivatized with PEG of an appropriate M(w) might be useful antitumor agent with protracted activity.