Tailoring Encodable Lanthanide‐Binding Tags as MRI Contrast Agents

Lanthanide‐binding tags (LBTs), peptide‐based coexpression tags with high affinity for lanthanide ions, have previously been applied as luminescent probes to provide phasing for structure determination in X‐ray crystallography and to provide restraints for structural refinement and distance information in NMR. The native affinity of LBTs for Gd³⁺ indicates their potential as the basis for engineering of peptide‐based MRI agents. However, the lanthanide coordination state that enhances luminescence and affords tightest binding would not be ideal for applications of LBTs as contrast agents, due to the exclusion of water from the inner coordination sphere. Herein, we use structurally defined LBTs as the starting point for re‐engineering the first coordination shell of the lanthanide ion to provide for high contrast through direct coordination of water to Gd³⁺ (resulting in the single LBT peptide, m‐sLBT). The effectiveness of LBTs as MRI contrast agents was examined in vitro through measurement of binding affinity and proton relaxivity. For imaging applications that require targeted observation, fusion to specific protein partners is desirable. However, a fusion protein comprising a concatenated double LBT (dLBT) as an N‐terminal tag for the model protein ubiquitin had reduced relaxivity compared with the free dLBT peptide. This limitation was overcome by the use of a construct based on the m‐sLBT sequence (q‐dLBT–ubiquitin). The structural basis for the enhanced contrast was examined by comparison of the X‐ray crystal structure of xq‐dLBT–ubiquitin (wherein two tryptophan residues are replaced with serine), to that of dLBT‐ubiquitin. The structure shows that the backbone conformational dynamics of the MRI variant may allow enhanced water exchange. This engineered LBT represents a first step in expanding the current base of specificity‐targeted agents available.     

靶向性磁共振成像造影剂的研究进展

综述了靶向性磁共振成像造影剂的研究进展,着重介绍了近年来在设计与合成具有靶向给药功能造影剂的研究概况,分别列出了亲脂性基团、VB6族化合物及其衍生物、糖类等功能基团作为靶向基团的水溶性顺磁性造影剂的配体结构。     

Development of intravascular contrast agents for MRI using gadolinium chelates

Two MRI contrast agents (CAs) composed of Gd‐DO3A conjugated to amino acid building blocks derived from glutamic acid ( CA1 ) and lysine ( CA2 ) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mM . The longitudinal relaxivities (r₁) of CA1 and CA2 measured at 9.4 T are 6.4 and 5.4 mM ^?1 s^?1 in H₂O at 25 °C, respectively. Both r₁ values are higher than those of CAs in clinical use: Gd‐DTPA (Magnevist, Bayer Schering, Germany) and Gd‐DOTA (Dotarem, Guerbet, France). In vivo imaging in Wistar rats demonstrated considerable signal enhancement (～50 %) in the brain artery by CA2 , but lower signal enhancement (～30 %) by CA1 . In contrast to Dotarem, which showed a similar signal enhancement as CA2 , the enhancement by CA2 remained high (～30 %), even at 52 min post‐injection. This demonstrates that CA2 has a much longer blood half‐life (68.1 min), which could be advantageous for angiography and tissue targeting.     

pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI

Acid-base homeostasis is an essential process for maintaining proper pH levels in the body, with alterations in this process potentially signaling pathology. While monitoring urine pH, blood gases and other assays can provide information on the overall systemic pH, it is desirable to get more localized knowledge to assist diagnosis. Various non-invasive methods have been developed with Chemical Exchange Saturation Transfer (CEST) MRI now emerging as a particularly intriguing technology for detecting pH. In this review, we provide an overview of the paramagnetic and diamagnetic CEST probes available for producing pH maps, describe in depth the various methods to collect CEST MRI data and post-process the resulting images to create pH maps and describe how this has been applied for detecting renal injury, mapping the pH of tumors and monitoring the health of transplanted therapeutic cells. Finally, we will provide an outlook of the possibilities to translate this technology into patients.     

Recent Advances in Strategies for Imaging Detection and Intervention of Cellular Senescence

Cellular senescence is a stable cell cycle arrest state that can be triggered by a wide range of intrinsic or extrinsic stresses. Increased burden of senescent cells in various tissues is thought to contribute to aging and age-related diseases. Thus, the detection and interventions of senescent cells are critical for longevity and treatment of disease. However, the highly heterogeneous feature of senescence makes it challenging for precise detection and selective clearance of senescent cells in different age-related diseases. To address this issue, considerable efforts have been devoted to developing senescence-targeting molecular theranostic strategies, based on the potential biomarkers of cellular senescence. Herein, we review recent advances in the field of anti-senescence research and highlight the specific visualization and elimination of senescent cells. Additionally, the challenges in this emerging field are outlined.     

Ingestible Contrast Agents for Gastrointestinal Imaging

Gastrointestinal (GI) ailments cover a wide variety of diseases involving the esophagus, stomach, small intestine, large intestine, and rectum. They bring about many inconveniences in daily life in chronic diseases and can even be life threatening in acute cases. Rapid and safe detection approaches are essential for early diagnosis and timely management. Contrast agents for GI imaging can enhance contrast to distinguish abnormal lesions from normal structures. Computed tomography and magnetic resonance imaging are two important diagnostic tools for the evaluation of GI conditions. This review mainly involves several common GI diseases, including inflammatory diseases, intestinal tumors, diarrhea, constipation, and gastroesophageal reflux diseases. Selected contrast agents, such as barium sulfate, iodine-based agents, gadolinium-based agents, and others, are summarized. Going forward, continued endeavors are being made to develop more emerging contrast agents for other imaging modalities.     

Synthesis and evaluation of paramagnetic particulates as contrast agents for magnetic resonance imaging (MRI)

Formulations based on novel particulate ion-exchange resins, containing a wide range of paramagnetic transition and rare-earth metals bound to their surfaces, have been synthesised as potential contrast agents for the magnetic resonance imaging (MRI) of the gastro-intestinal (GI) tract of man. They have been evaluated in terms of their effects upon the spin-lattice (R₁) and spin-spin (R₂) relaxation rates of the protons of water. Careful selection of the polymer, spacer-arm, ligand and paramagnetic ion provides a means for subtle molecular tailoring. Further potential applications have been highlighted based on the observed properties of such formulations.     

Reporter Genes for Brain Imaging Using MRI,SPECT and PET

The use of molecular imaging technologies for brain imaging can not only play an important supporting role in disease diagnosis and treatment but can also be used to deeply study brain functions. Recently, with the support of reporter gene technology, optical imaging has achieved a breakthrough in brain function studies at the molecular level. Reporter gene technology based on traditional clinical imaging modalities is also expanding. By benefiting from the deeper imaging depths and wider imaging ranges now possible, these methods have led to breakthroughs in preclinical and clinical research. This article focuses on the applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies for use in brain imaging. The tracking of cell therapies and gene therapies is the most successful and widely used application of these techniques. Meanwhile, breakthroughs have been achieved in the research and development of reporter genes and their imaging probe pairs with respect to brain function research. This paper introduces the imaging principles and classifications of the reporter gene technologies of these imaging modalities, lists the relevant brain imaging applications, reviews their characteristics, and discusses the opportunities and challenges faced by clinical imaging modalities based on reporter gene technology. The conclusion is provided in the last section.     

Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.     

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are based on γ-emissions of specific energies. The therapeutic technologies are based on β⁻-particle-, α-particle-, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease‘s progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost-efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.     

Recent Advances in Flame Tomographyt

To reduce greenhouse gas emissions from fossil fuel fired power plants,a range of new combustion technologies are being developed or refined,including oxy-fuel combustion,co-firing biomass with coal and fluidized bed combustion.Flame characteristics under such combustion conditions are expected to b     

火焰层析成像的最新进展(英文)

To reduce greenhouse gas emissions from fossil fuel fired power plants,a range of new combustion technologies are being developed or refined,including oxy-fuel combustion,co-firing biomass with coal and fluidized bed combustion.Flame characteristics under such combustion conditions are expected to be different from those in normal air fired combustion processes.Quantified flame characteristics such as temperature distribution,oscillation frequency,and ignition volume play an important part in the optimized design and operation of the environmentally friendly power generation systems.However,it is challenging to obtain such flame characteristics particularly through a three-dimensional and non-intrusive means.Various tomography methods have been proposed to visualize and characterize flames,including passive optical tomography,laser based tomography,and electrical tomography.This paper identifies the challenges in flame tomography and reviews existing techniques for the quantitative characterization of flames.Future trends in flame tomography for industrial applications are discussed.     

In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.     

含钛分子筛合成研究的新进展

本文综述了具有独特氧化性能的含钛分子筛合成研究新进展,探讨了在合成TS-1和TS-2沸石中不同硅源、钛源、模板剂及合成路线对其结构性能的影响,评述了Ti-MCM-4、Ti-TMS、Ti-β型等含钛沸石的合成技术。     

Recent Advances in Neuraminidase Inhibitor Development as Anti-influenza Drugs

The recent emergence of the highly pathogenic H5N1 subtype of avian influenza virus (AIV) and of the new type of human influenza A (H1N1) have emphasized the need for the development of effective anti‐influenza drugs. Presently, neuraminidase (NA) inhibitors are widely used in the treatment and prophylaxis of human influenza virus infection, and tremendous efforts have been made to develop more potent NA inhibitors to combat resistance and new influenza viruses. In this review, we discuss the structural characteristics of NA catalytic domains and the recent developments of new NA inhibitors using structure‐based drug design strategies. These drugs include analogues of zanamivir, analogues of oseltamivir, analogues of peramivir, and analogues of aromatic carboxylic acid and present promising options for therapeutics or leads for further development of NA inhibitors that may be useful in the event of a future influenza pandemic.     

19F MRI Nanotheranostics for Cancer Management: Progress and Prospects

Fluorine magnetic resonance imaging (¹⁹F MRI) is a promising imaging technique for cancer diagnosis because of its excellent soft tissue resolution and deep tissue penetration, as well as the inherent high natural abundance, almost no endogenous interference, quantitative analysis, and wide chemical shift range of the ¹⁹F nucleus. In recent years, scientists have synthesized various ¹⁹F MRI contrast agents. By further integrating a wide variety of nanomaterials and cutting-edge construction strategies, magnetically equivalent ¹⁹F atoms are super-loaded and maintain satisfactory relaxation efficiency to obtain high-intensity ¹⁹F MRI signals. In this review, the nuclear magnetic resonance principle underlying ¹⁹F MRI is first described. Then, the construction and performance of various fluorinated contrast agents are summarized. Finally, challenges and future prospects regarding the clinical translation of ¹⁹F MRI nanoprobes are considered. This review will provide strategic guidance and panoramic expectations for designing new cancer theranostic regimens and realizing their clinical translation.     

新结构沸石分子筛

综述了从１９９６年４月至今国际沸石学会认定的２８种新结构分子筛的结构特征、化学组成、合成所用的模板剂及其应用开发。     

Recent Advances in Hydrogen Peroxide Responsive Organoborons for Biological and Biomedical Applications

Hydrogen peroxide is the most stable reactive oxygen species generated endogenously, participating in numerous physiological processes and abnormal pathological conditions. Mounting evidence suggests that a higher level of H₂O₂ exists in various disease conditions. Thus, H₂O₂ functions as an ideal target for site-specific bioimaging and therapeutic targeting. The unique reactivity of organoborons with H₂O₂ provides a method for developing chemoselective molecules for biological and biomedical applications. This review highlights the design and application of boron-derived molecules for H₂O₂ detection, and the utility of boron moieties toward masking reactive compounds leading to the development of metal prochelators and prodrugs for selectively delivering an active species at the target sites with elevated H₂O₂ levels. Additionally, the emergence of H₂O₂-responsive theranostic agents consisting of both therapeutic and diagnostic moieties in one integrated system are discussed. The purpose of this review is to provide a better understanding of the role of boron-derived molecules toward biological and pharmacological applications.