Tumor Imaging Applications Research Articles

Surface-engineered core-shell upconversion nanoparticles for effective hypericin delivery and multimodal imaging.

Early diagnosis and treatment of cancer is rapidly advancing thanks to the development of nanotechnology. Here, upconversion nanoparticles (UCNPs) are particularly promising as they are finding a wide range of applications in drug delivery and tumor imaging. In this report, a novel UCNP-based transport system is proposed for the delivery of the hypericin (Hyp) photosensitizer into malignant tumors. Core-shell NaYF4:Yb3+,Er3+@NaYF4:Nd3+ UCNPs were prepared by thermal decomposition and coated with poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate)-alendronate [P(DMA-AEA)-Ale], which endowed them with colloidal and chemical stability; finally, Hyp was conjugated. Internalization of CS-UCNP@P(DMA-AEA)-Ale-Hyp nanoparticles by Jurkat cells was successfully validated by multimodal imaging using a microstructural chamber, upconversion luminescence, and Raman microspectroscopy. After irradiation at 590 nm, CS-UCNP@P(DMA-AEA)-Ale-Hyp nanoparticles provided a markedly more effective photodynamic effect than Hyp alone at identical Hyp concentrations due to apoptosis as confirmed by caspase-3 activation. MTT assays showed that Hyp-free nanoparticles were non-cytotoxic, whereas CS-UCNP@P(DMA-AEA)-Ale-Hyp particles significantly reduced cell viability after irradiation. Considering that Hyp release from the nanoparticles was higher in the acidic environment typical of tumors compared to physiological ones, UCNP@P(DMA-AEA)-Ale-Hyp particles are a suitable candidate for future in vivo applications.

NIR AIE luminogens for primary and metastasis tumor imaging and tracking applications

Modern lifestyle changes, including irregular diets and late-night activities, have contributed to a significant rise in cancer rates, particularly among younger demographics, highlighting the pressing need for early detection and treatment.

Design and synthesis of fluorescent BODIPY derivatives with D-A structure for cancer cell imaging

Boron-dipyrromethene (BODIPY) as a traditional fluorescent dye has received increasing attention because of its high molar extinction coefficient, easy modification, and good light stability. In this work, three BODIPY compounds (BDP-1, BDP-2 and BDP-3) were designed and synthesized by introducing PEG chains and a naphthalimide (NI) group onto the parent structure of BODIPY. Due to the electron-withdrawing properties of NI, the compounds of BDP-2 and BDP-3 formed a typical donor (D)-acceptor (A) structure, which led to the red-shifted absorption and fluorescence spectrum. The synthesized BODIPY exhibited intense green emission, with fluorescence quantum yield of 0.66, 0.29, and 0.19 for BDP-1, BDP-2 and BDP-3 respectively. The decrease in fluorescence of BDP-2 and BDP-3 was probably ascribed to the enhanced intramolecular charge transfer because of the introduction of the NI group. The good biocompatibility and low cytotoxicity of the synthesized BODIPY compounds were verified by the CCK-8 assay. The subcellular localization of the three compounds was further evaluated through a confocal laser scanning microscope. The results showed that these BODIPY derivatives were mainly localized in the lysosomes of cancer cells. Thus, the synthesized BODIPY fluorescent dyes show promising applications in tumor imaging benefiting from their good biocompatibility and strong fluorescence.

In vivo tumor imaging and therapy based on near-infrared cadmium-free quantum dots

Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging in vivo and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging in vivo and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.

Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging

BackgroundThe polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. ResultsThe radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64–69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71. ConclusionThese results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.

The family of pH (Low) Insertion Peptides (pHLIP) comprises a tumor-agnostic technology that uses the low pH (or high acidity) at the surfaces of cells within the tumor microenvironment (TME) as a targeted biomarker. pHLIPs can be used for extracellular and intracellular delivery of a variety of imaging and therapeutic payloads. Unlike therapeutic delivery targeted to specific receptors on the surfaces of particular cells, pHLIP targets cancer, stromal and some immune cells all at once. Since the TME exhibits complex cellular crosstalk interactions, simultaneous targeting and delivery to different cell types leads to a significant synergistic effect for many agents. pHLIPs can also be positioned on the surfaces of various nanoparticles (NPs) for the targeted intracellular delivery of encapsulated payloads. The pHLIP technology is currently advancing in pre-clinical and clinical applications for tumor imaging and treatment.

Bone tumors: state-of-the-art imaging.

Imaging plays a central role in the management of patients with bone tumors. A number of imaging modalities are available, with different techniques having unique applications that render their use advantageous for various clinical purposes. Coupled with detailed clinical assessment, radiological imaging can assist clinicians in reaching a proper diagnosis, determining appropriate management, evaluating response to treatment, and monitoring for tumor recurrence. Although radiography is still the initial imaging test of choice for a patient presenting with a suspected bone tumor, technological innovations in the last decades have advanced the role of other imaging modalities for assessing bone tumors, including advances in computed tomography, magnetic resonance imaging, scintigraphy, and hybrid imaging techniques that combine two existing modalities, providing clinicians with diverse tools for bone tumor imaging applications. Determining the most suitable modality to use for a particular application requires familiarity with the modality in question, its advancements, and its limitations. This review highlights the various imaging techniques currently available and emphasizes the latest developments in imaging, offering a framework that can help guide the imaging of patients with bone tumors.

Development of novel radiolabeled antibody-conjugated graphene quantum dots for targeted in vivo breast cancer imaging and biodistribution studies

Nanotechnology-based drug delivery platforms have emerged as one of the promising approaches for the diagnosis and treatment of cancers. Furthermore, significant advancements have been achieved in the development of nanoparticle-antibody conjugates for applications in tumor imaging and immunoassays. Without a doubt, the diagnostic insight garnered from these nanoprobes will prove invaluable in determining rational therapeutic strategies. In the current experiment, we developed a breast cancer imaging probe utilizing graphene quantum dots, these quantum dots were conjugated with pembrolizumab (GQDs–pembrolizumab), a human monoclonal antibody (mAb) targeting the immune checkpoint programmed death receptor (PD-1) and its programmed death ligand-1 (PD-L1). Various techniques were employed for characterization, encompassing transmission electron microscopy (TEM), element mapping, atomic force microscopy (AFM), Fourier-transform infrared spectroscopy, and circular dichroism (CD) spectroscopy. The toxicity of nanoconjugate was evaluated using the MTT assay on HEK-293 and 4T1 cell lines. Subsequently, the synthesized nanoconjugate was radiolabeled with Technetium-99m (99mTc) to produce 99mTc-GQDs–pembrolizumab. Biodistribution and SPECT imaging were conducted to assess the pharmacokinetics and targeting efficacy of the 99mTc-GQDs–pembrolizumab in a BALB/c mouse model bearing with 4T1 tumors. The high Radiochemical purity (RCP > 95 %) and satisfactory in vitro stability demonstrate the significant potential of GQDs–pembrolizumab to form complexes with Technetium-99m. The findings from imaging and biodistribution studies demonstrated the high activity of 99mTc-GQDs–pembrolizumab at the tumor site (8.4 %ID/g), attributed to the presence of the PD-1 receptor. Furthermore, the increased radiotracer uptake was evident in the liver and spleen, both being lymphoid tissues. The suitable properties and behavior of 99mTc-GQDs–pembrolizumab suggest that it holds promise as a novel probe for the development of radiopharmaceutical-based immune checkpoint monoclonal antibodies. Additionally, it has the potential to facilitate immunotherapy for treating a wide range of cancers.

Effect of Hollow Structures on T1 and T2 Relaxivities and Their Application in Accurate Tumor Imaging

Effect of Hollow Structures on <i>T</i>₁ and <i>T</i>₂ Relaxivities and Their Application in Accurate Tumor Imaging

Peptides Targeting HER2-Positive Breast Cancer Cells and Applications in Tumor Imaging and Delivery of Chemotherapeutics.

Breast cancer represents the most common cancer type and one of the major leading causes of death in the female worldwide population. Overexpression of HER2, a transmembrane glycoprotein related to the epidermal growth factor receptor, results in a biologically and clinically aggressive breast cancer subtype. It is also the primary driver for tumor detection and progression and, in addition to being an important prognostic factor in women diagnosed with breast cancer, HER2 is a widely known therapeutic target for drug development. The aim of this review is to provide an updated overview of the main approaches for the diagnosis and treatment of HER2-positive breast cancer proposed in the literature over the past decade. We focused on the different targeting strategies involving antibodies and peptides that have been explored with their relative outcomes and current limitations that need to be improved. The review also encompasses a discussion on targeted peptides acting as probes for molecular imaging. By using different types of HER2-targeting strategies, nanotechnology promises to overcome some of the current clinical challenges by developing novel HER2-guided nanosystems suitable as powerful tools in breast cancer imaging, targeting, and therapy.

A high affinity and specificity anti-HER2 single-domain antibody (VHH) that targets trastuzumab's epitope with versatile biochemical, biological, and medical applications.

In the past decade, various single-domain antibodies from llamas, also known as VHH or nanobody, have been discovered with applications in tumor imaging and cancer therapy. However, the potential application of anti-HER2 VHHs as a diagnostic tool suitable for ELISA, flow cytometry, cell imaging, bispecific antibody engineering,and immunohistochemistry has not been fully elucidated. To investigate this potential, HER2 antigen was expressed in HEK293 F cells, purified, and used to immunize llama. Using phage display, anti-HER2 VHHs with high affinity and specificity were isolated, sequenced, and constructed with a Histag and c-Myc tag. The constructed anti-HER2 VHHs were then expressed in E. coli, purified, and evaluated for their use in ELISA, flow cytometry, cell imaging, and immunohistochemistry. The affinities of the anti-HER2 VHHs toward the HER2 antigen were determined using biolayer interferometry. Furthermore, the binding sites of the anti-HER2 VHHs were evaluated by epitope mapping and in silico modeling and docking. Here, we report the sequence of an anti-HER2 VHH with high affinity (sub-nanomolar), specificity, and selectivity. This VHH binds to the same epitope as trastuzumab and can be utilized to generate bispecific antibodies or used as a diagnostic tool to differentiate HER2+ from HER2- antigens on plates, cells, and tissues. This discovery has broad applications in biochemical, biological, and medical sciences.

Unexcited Light Source Imaging for Biomedical Applications.

Optical imaging has a wide range of applications in the biomedical field, allowing the visualization of physiological processes and helping in the diagnosis and treatment of diseases. Unexcited light source imaging technologies, such as chemiluminescence imaging, bioluminescence imaging and afterglow imaging have attracted great attention in recent years because of the absence of excitation light interference in their application and the advantages of high sensitivity and high signal-to-noise ratio. In this review, the latest advances in unexcited light source imaging technology for biomedical applications are highlighted. The design strategies of unexcited light source luminescent probes in improving luminescence brightness, penetration depth, quantum yield and targeting, and their applications in inflammation imaging, tumor imaging, liver and kidney injury imaging and bacterial infection imaging are introduced in detail. The research progress and future prospects of unexcited light source imaging for medical applications are further discussed.

Reaction mechanism of nanomedicine based on porphyrin skeleton and its application prospects.

Research on porphyrin-based photosensitizing drugs is becoming increasingly popular. They possess unique diagnostic capabilities and therapeutic effects that have gained wide recognition in oncology drug development. In recent years, the rapid growth of nanotechnology has brought great hope for nanopharmaceutical formulations. By combining porphyrins with various nanomaterials, people have improved the properties of porphyrin compounds, making drug delivery easier. Porphyrin-based nanoparticles can enhance the effect of photodynamic therapy for cancer treatment, providing opportunities for achieving complex targeting strategies and versatility with promising applications in drug carriers, tumor imaging, and treatment. This paper reviews recent porphyrin nanodrugs, including inorganic-organic hybrid nanoparticles, nanomicelles, self-assembled nanoparticles, and combination therapeutic nanodrugs, and their actions and effects on cancer cells when performing photodynamic therapy. It also discusses the drawbacks as well as the prospects for development.

Radiomics Applications in Head and Neck Tumor Imaging: A Narrative Review.

Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, prognosis and therapy recommendation are given special consideration. In a narrative manner, we outline the fundamental technological principles, the overall idea and usual workflow of radiomic analysis and what seem to be the present and potential challenges in normal clinical practice. Clinical oncology intends for all of this to ensure informed decision support for personalized and useful cancer treatment. Head and neck cancers present a unique set of diagnostic and therapeutic challenges. These challenges are brought on by the complicated anatomy and heterogeneity of the area under investigation. Radiomics has the potential to address these barriers. Future research must be interdisciplinary and focus on the study of certain oncologic functions and outcomes, with external validation and multi-institutional cooperation in order to achieve this.

Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging

BackgroundUltrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents.MethodsSuperparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed.ResultsThe synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn’t change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging.ConclusionThese data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.

Biodegradable nanomaterials for diagnosis and therapy of tumors.

Although degradable nanomaterials have been widely designed and applied for cancer bioimaging and various cancer treatments, few reviews of biodegradable nanomaterials have been reported. Herein, we have summarized the representative research advances of biodegradable nanomaterials with respect to the mechanism of degradation and their application in tumor imaging and therapy. First, four kinds of tumor microenvironment (TME) responsive degradation are presented, including pH, glutathione (GSH), hypoxia and matrix metalloproteinase (MMP) responsive degradation. Second, external stimulation degradation is summarized briefly. Next, we have outlined the applications of nanomaterials in bioimaging. Finally, we have focused on some typical examples of biodegradable nanomaterials in radiotherapy (RT), photothermal therapy (PTT), starvation therapy, photodynamic therapy (PDT), chemotherapy, chemodynamic therapy (CDT), sonodynamic therapy (SDT), gene therapy, immunotherapy and combination therapy.

A tumor-targetable NIR probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy.

Spatiotemporally manipulating the in situ immobilization of theranostic agents within cancer cells to improve their bioavailability is highly significant yet challenging in tumor diagnosis and treatment. Herein, as a proof-of concept, we for the first time report a tumor-targetable near-infrared (NIR) probe DACF with photoaffinity crosslinking characteristics for enhanced tumor imaging and therapeutic applications. This probe possesses great tumor-targeting capability, intensive NIR/photoacoustic (PA) signals, and a predominant photothermal effect, allowing for sensitive imaging and effective photothermal therapy (PTT) of tumors. Most notably, upon 405 nm laser illumination, DACF could be covalently immobilized within tumor cells through a photocrosslinking reaction between photolabile diazirine groups and surrounding biomolecules resulting in enhanced tumor accumulation and prolonged retention simultaneously, which significantly facilitates the imaging and PTT efficacy of tumor in vivo. We therefore believe that our current approach would provide a new insight for achieving precise cancer theranostics.

Sensor-to-Image Based Neural Networks: A Reliable Reconstruction Method for Diffuse Optical Imaging of High-Scattering Media

Imaging tasks today are being increasingly shifted toward deep learning-based solutions. Biomedical imaging problems are no exception toward this tendency. It is appealing to consider deep learning as an alternative to such a complex imaging task. Although research of deep learning-based solutions continues to thrive, challenges still remain that limits the availability of these solutions in clinical practice. Diffuse optical tomography is a particularly challenging field since the problem is both ill-posed and ill-conditioned. To get a reconstructed image, various regularization-based models and procedures have been developed in the last three decades. In this study, a sensor-to-image based neural network for diffuse optical imaging has been developed as an alternative to the existing Tikhonov regularization (TR) method. It also provides a different structure compared to previous neural network approaches. We focus on realizing a complete image reconstruction function approximation (from sensor to image) by combining multiple deep learning architectures known in imaging fields that gives more capability to learn than the fully connected neural networks (FCNN) and/or convolutional neural networks (CNN) architectures. We use the idea of transformation from sensor- to image-domain similarly with AUTOMAP, and use the concept of an encoder, which is to learn a compressed representation of the inputs. Further, a U-net with skip connections to extract features and obtain the contrast image, is proposed and implemented. We designed a branching-like structure of the network that fully supports the ring-scanning measurement system, which means it can deal with various types of experimental data. The output images are obtained by multiplying the contrast images with the background coefficients. Our network is capable of producing attainable performance in both simulation and experiment cases, and is proven to be reliable to reconstruct non-synthesized data. Its apparent superior performance was compared with the results of the TR method and FCNN models. The proposed and implemented model is feasible to localize the inclusions with various conditions. The strategy created in this paper can be a promising alternative solution for clinical breast tumor imaging applications.

A water-soluble fluorescent probe for the determination of γ-glutamyltransferase activity and its application in tumor imaging

γ-glutamyltransferase (GGT), an important tumor marker, is highly expressed in tumor tissues, and precise detection of its activity provides a vital indicator for the diagnosis and treatment. In this work, a “lighting-on” probe (TCF-GGT) was elaborated to detect endogenous GGT with high selectivity and sensitivity. Dicyanomethyldifuranyl (TCF-OH) was employed as the fluorescence reporter and short peptide glutathione (GSH) worked as the GGT-active trigger, the introduction of which prevented the initial proton transfer of TCF-OH contributing to a blank sensing background. A bright red fluorescence could be switched on upon GGT catalytic hydrolysis, avoiding the potential interference from background. There displayed an excellent water-solubility, and little organic solvent was required during the exploration, which otherwise avoided the potential damage to enzyme and organism. TCF-GGT has been proved to be workable at cellular and organism level with highly effective imaging and a short metabolic cycle, which is expected to offer an alternative solution or reference to the early diagnosis and treatment of tumor.

Nanoscale Zeolitic Imidazolate Framework (ZIF)–8 in Cancer Theranostics: Current Challenges and Prospects

Simple SummaryThe biomedical application of metal–organic frameworks in cancer theranostics has become a research hotspot with rapid progress. As a typical representative, ZIF–8 attracts increasing interest from researchers due to its good performance and potential. In this review, we updated recent discoveries on the ZIF–8–based nanoplatforms for cancer, discussed the problems in current research and the obstacles for clinical translation of ZIF–8, and also proposed an outlook on its future development.Cancer severely threatens human health and has remained the leading cause of disease–related death for decades. With the rapid advancement of nanomedicine, nanoscale metal–organic frameworks are believed to be potentially applied in the treatment and biomedical imaging for various tumors. Zeolite imidazole framework (ZIF)–8 attracts increasing attention due to its high porosity, large specific surface area, and pH–responsiveness. The designs and modifications of ZIF–8 nanoparticles, as well as the strategy of drug loading, demand a multifaceted and comprehensive understanding of nanomaterial features and tumor characteristics. We searched for studies on ZIF–8–based nanoplatforms in tumor theranostics on Web of Science from 2015 to 2022, mainly focused on the research published in the past 3 years, summarized the progress of their applications in tumor imaging and treatment, and discussed the favorable aspects of ZIF–8 nanoparticles for tumor theranostics as well as the future opportunities and potential challenges. As a kind of metal–organic framework material full of potential, ZIF–8 can be expected to be combined with more therapeutic systems in the future and continue to contribute to all aspects of tumor therapy and diagnosis.