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Aleukemic leukemia cutis (ALC) is a rare condition with a relatively poor prognosis, clinically presenting as skin and subcutaneous nodules commonly involving head and neck region with discrete atypical leukemic cells infiltrating in the skin on histopathology. The lesions on the genital area skin are seldom reported. A 49-year-old male presented with joint pains and multiple subcutaneous nodules clinically with biopsy proving it as leukemia cutis. Bone marrow aspiration and biopsy were suggestive of normocellular myeloid preponderant bone marrow with mild increase in eosinophils. The 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) revealed metabolically active FDG avid ill-defined soft tissue attenuation involving the entire length of penile shaft with central necrotic area, diffuse scrota skin thickening, and lateral compartment muscles of left leg, in addition to multiple hypermetabolic metastatic lymph nodes, and diffuse hypermetabolic marrow in humerii and femora. Despite prompt investigations and initiation of management, the patient succumbed in 15 days post-FDG PET/CT. The present report depicts an atypical case of ALC, with FDG PET-CT showing extensive and unusual sites of disease involvement, emphasizing its potential role in ALC. [ABSTRACT FROM AUTHOR]

Tyrosine‐protein kinase Met—also known as c‐Met or HGFR—is a membrane receptor protein with associated tyrosine kinase activity physiologically stimulated by its natural ligand, the hepatocyte growth factor (HGF), and is involved in different ways in cancer progression and tumourigenesis. Targeting c‐Met with pharmaceuticals has been preclinically proved to have significant benefits for cancer treatment. Recently, evaluating the protein status during and before c‐Met targeted therapy has been shown of relevant importance by different studies, demonstrating that there is a correlation between the status (e.g., aberrant activation and overexpression) of the HGFR with therapy response and clinical prognosis. Currently, clinical imaging based on positron emission tomography (PET) appears as one of the most promising tools for the in vivo real‐time scanning of irregular alterations of the tyrosine‐protein kinase Met and for the diagnosis of c‐Met related cancers. In this study, we review the recent progress in the imaging of c‐Met aberrant cancers with PET. Particular attention is directed on the development of PET probes with a range of different sizes (HGF, antibodies, anticalines, peptides, and small molecules), and radiolabeled with different radionuclides. The goal of this review is to report all the preclinical imaging studies based on PET imaging reported until now for in vivo diagnosis of c‐Met in oncology to support the design of novel and more effective PET probes for in vivo evaluation of c‐Met. [ABSTRACT FROM AUTHOR]

Copper‐based nanomaterials (Cu‐based NMs) with favorable biocompatibility and unique properties have attracted the attention of many biomedical researchers. Cu‐based NMs are one of the most widely studied materials in cancer treatment. In recent years, great progress has been made in the field of biomedicine, especially in the treatment and diagnosis of tumors. This review begins with the classification of Cu‐based NMs and the recent synthetic strategies of Cu‐based NMs. Then, according to the abundant and special properties of Cu‐based NMs, their application in biomedicine is summarized in detail. For biomedical imaging, such as photoacoustic imaging, positron emission tomography imaging, and multimodal imaging based on Cu‐based NMs are summarized, as well as strategies to improve the diagnostic effectiveness. Moreover, a series of unique structures and functions as well as the underlying property activity relationship of Cu‐based NMs were shown to highlight their promising therapeutic performance. Cu‐based NMs have been widely used in monotherapies, such as photothermal therapy (PTT) and chemodynamic therapy (CDT). Moreover, the sophisticated design in composition, structure, and surface fabrication of Cu‐based NMs can endow these NMs with more modalities in cancer diagnosis and therapy. To further improve the efficiency of cancer treatment, combined therapy based on Cu‐based NMs was introduced in detail. Finally, the challenges, critical factors, and future prospects for the clinical translation of Cu‐based NMs as multifunctional theranostic agents were also considered and discussed. The aim of this review is to provide a better understanding and key consideration for the rational design of this increasingly important new paradigm of Cu‐based NMs as theranostic agents. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseDiagnostic Tools > In Vivo Nanodiagnostics and Imaging [ABSTRACT FROM AUTHOR]

The present study focuses on the development of a sensitive and specific approach for the visualization of sentinel lymph nodes draining the tumor using ultrabright 200‐nm fluorescent nanodiamonds (FNDs) equipped with a designed targeting surface architecture. The FNDs with a narrow size distribution are isolated by differential centrifugation, colloidally stabilized with alkyne‐functionalized poly(glycerol) and modified with a polyvalent array of mannose (FND‐p‐Man). In vitro experiments demonstrate an outstanding increase of the particle internalization by the mannose receptor CD206 (MR) and no significant toxicity. MR involvement is confirmed by blocking ligand binding with mannan and a 15.2 mAb (specific anti‐MR) in J774A.1 mouse macrophage cell line. In vivo mouse experiments confirm increased retention of FND‐p‐Man in sentinel lymph nodes of both healthy and B16 melanoma bearing animals. These results suggest that FND‐p‐Man has potential as a tracer for lymph node visualization in locoregional perioperative cancer diagnostics and as a tool for endoscopic/robotic fluorescence‐guided surgery. [ABSTRACT FROM AUTHOR]

PD-L1 (programmed death-ligand 1) targeted therapies may be useful for several cancers. The use of non-invasive diagnostic and prognostic molecular imaging platforms could improve clinical assessment of PD-L1 tumor status during these therapies. Contrast enhanced ultrasound molecular imaging (CE-USMI) techniques may offer versatile and cost-effective ways to detect and quantify the expression levels of cellular targets in vivo. However, conventional use of microbubbles as a blood pool contrast agent for CE-USMI is limited to accessing intravascular biomarkers rather than reflecting the tumor molecular status. Using a microfluidic based reconstruction process we therefore developed ultra-stable nanobubbles (NBs) as a contrast agent for molecular imaging of vascular and extravascular cell surface markers. We then functionalized these NBs by covalently linking to nanobody (FN3 hPD-L1) targeting human (h)PD-L1 to measure the expression of human PD-L1 in the tumor microenvironment (TME) in vivo. We showed the specific binding of hPD-L1 targeted NBs in cell culture, and in xenografted mouse models of hPD-L1 expressing CT26 tumors. CE-USMI of hPD-L1 in the TME in vivo showed ~3-fold increase in contrast signal compared to non-targeted NBs. Overall, in vivo use of CE-USMI with hPD-L1 targeted NBs has the potential for clinical translation and imaging of human cancers during immunotherapy, and for prognostic evaluation of patient response to PD-L1 targeted immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Imaging has become an invaluable tool in preclinical research for its capability to non-invasively detect and monitor disease and assess treatment response. With the increased use of preclinical imaging, large volumes of image data are being generated requiring critical data management tools. Due to proprietary issues and continuous technology development, preclinical images, unlike DICOM-based images, are often stored in an unstructured data file in company-specific proprietary formats. This limits the available DICOM-based image management database to be effectively used for preclinical applications. A centralized image registry and management tool is essential for advances in preclinical imaging research. Specifically, such tools may have a high impact in generating large image datasets for the evolving artificial intelligence applications and performing retrospective analyses of previously acquired images. In this study, a web-based server application is developed to address some of these issues. The application is designed to reflect the actual experimentation workflow maintaining detailed records of both individual images and experimental data relevant to specific studies and/or projects. The application also includes a web-based 3D/4D image viewer to easily and quickly view and evaluate images. This paper briefly describes the initial implementation of the web-based application. [ABSTRACT FROM AUTHOR]

Recent technical advances in positron emission tomography/magnetic resonance imaging (PET/MRI) technology allow much improved time-of-flight (TOF) and regularized iterative PET reconstruction regularized iterative reconstruction (RIR) algorithms. We evaluated the effect of TOF and RIR on standardized uptake values (maximum and peak SUV [SUVmax and SUVpeak]) and their metabolic tumor volume dependencies and visual image quality for 18F-fluorocholine PET/MRI in patients with newly diagnosed prostate cancer. Fourteen patients were administered with 3 MBq/kg of 18F-fluorocholine and scanned dynamically for 30 minutes. Positron emission tomography images were divided to early and late time points (1-6 minutes summed and 7-30 minutes summed). The values of the different SUVs were documented for dominant PET-avid lesions, and metabolic tumor volume was estimated using a 50% isocontour and SUV threshold of 2.5. Image quality was assessed via visual acuity scoring (VAS). We found that incorporation of TOF or RIR increased lesion SUVs. The lesion to background ratio was not improved by TOF reconstruction, while RIR improved the lesion to background ratio significantly ( P < .05). The values of the different VAS were all significantly higher ( P < .05) for RIR images over TOF, RIR over non-TOF, and TOF over non-TOF. In conclusion, our data indicate that TOF or RIR should be incorporated into current protocols when available.

To investigate the impact of mono- and di-β-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1′-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were used as starting materials. Reaction of the intermediates containing one or two carboxylic acid functionalities with 1-aminogalactose afforded the desired 172- or 20(4′)- mono- and 172, 20(4′)-di galactose conjugated photosensitizers (PSs) with and without a carboxylic acid group. The overall lipophilicity caused by the presence of galactose in combination with either an ethyl or (1′-hexyloxy)ethyl side chain at position-3 of the macrocycle made a significant difference in in vitro uptake by tumor cells and photoreaction upon light exposure. Interestingly, among the PSs investigated, compared to HPPH 1 the carbohydrate conjugates 2 and 11 in which β-galactose moieties are conjugated at positions 172 and 20(4′) of meso-pyro pheophorbide-a showed similar in vitro efficacy in FaDu cell lines, but in SCID mice bearing FaDu tumors (head & neck) Ps 11 gave significantly improved long-term tumor cure.

Cancer biomechanical properties, including high stiffness, solid stress, and interstitial pressure, as well as altered micro-architecture, are drivers of tumorigenesis, invasiveness and resistance to treatment. Magnetic resonance elastography is an emergent non-invasive imaging method to assess the tumor mechanical properties in a spatially resolved fashion. Several MRE acquisition and reconstruction methods have been developed to assess tumors and surrounding tissues. It is increasingly recognized that the visco-elastic properties assessed with MRE are useful for characterizing malignant tumors and evaluating treatment response in various organs. Generally, malignant tumors, except brain tumors, have high stiffness and high visco-elastic ratio or fluidity. MRE transducers, acquisition sequences and reconstruction algorithms are continuously improved to increase depth penetration and spatial resolution, and limit artifacts at spatial discontinuities. Moreover, assessment of compression stiffening might provide new biomarkers of the altered physical traits of cancer. Increasing research and clinical validation will improve the efficacy of MRE for cancer characterization.

Optical coherence tomography (OCT) is a non-invasive imaging technique which has become the “gold standard” for diagnosis in the field of ophthalmology. However, in contrast to the eye, nontransparent tissues exhibit a high degree of optical scattering and absorption, resulting in a limited OCT imaging depth. And the progress made in the past decade in OCT technology have made it possible to image nontransparent tissues with high spatial resolution at large (up to 2mm) imaging depth. On the one hand, OCT can be used in a rapid, noninvasive way to detect diseased tissues, organs, blood vessels or glands. On the other hand, it can also identify the optical characteristics of suspicious parts in the early stage of the disease, which is of great significance for the early diagnosis of tumor diseases. Furthermore, OCT imaging has been explored for imaging tumor cells and their dynamics, and for the monitoring of tumor responses to treatments. This review summarizes the recent advances in the OCT area, which application in oncological diagnosis and treatment in different types: (1) superficial tumors:OCT could detect microscopic information on the skin’s surface at high resolution and has been demonstrated to help diagnose common skin cancers; (2) gastrointestinal tumors: OCT can be integrated into small probes and catheters to image the structure of the stomach wall, enabling the diagnosis and differentiation of gastrointestinal tumors and inflammation; (3) deep tumors: with the rapid development of OCT imaging technology, it has shown great potential in the diagnosis of deep tumors such in brain tumors, breast cancer, bladder cancer, and lung cancer.

Encoding the sodium iodide symporter (NIS) by an adenovirus (Ad) is a promising strategy to facilitate non-invasive imaging and radiotherapy of pancreatic cancer. However, insufficient levels of NIS expression in tumor cells have limited its clinical translation. To optimize Ad-based radiotherapy and imaging, we investigated the effect of Ad death protein (ADP) deletion on NIS expression. We cloned two sets of oncolytic NIS-expressing Ads that differed only in the presence or absence of ADP. We found that ADP expression negatively affected NIS membrane localization and inhibited radiotracer uptake. ADP deletion significantly improved NIS-based imaging in pancreatic cancer models including patient-derived xenografts, where effective imaging was possible for up to 6 weeks after a single virus injection. This study demonstrates that improved oncolysis may hinder the therapeutic effect of oncolytic viruses designed to express NIS. In vivo studies in combination with 131I showed potential for effective radiotherapy. This also highlights the need for further investigation into optimal timing of 131I administration and suggests that repeated doses of 131I should be considered to improve efficacy in clinical trials. We conclude that ADP deletion is essential for effective NIS-based theranostics in cancer.

The classification of gigapixel Whole Slide Images (WSIs) is an important task in the emerging area of computational pathology. There has been a surge of interest in deep learning models for WSI classification with clinical applications such as cancer detection or prediction of cellular mutations. Most supervised methods require expensive and labor-intensive manual annotations by expert pathologists. Weakly supervised Multiple Instance Learning (MIL) methods have recently demonstrated excellent performance; however, they still require large-scale slide-level labeled training datasets that require a careful inspection of each slide by an expert pathologist. In this work, we propose a fully unsupervised WSI classification algorithm based on mutual transformer learning. The instances (i.e., patches) from gigapixel WSIs are transformed into a latent space and then inverse-transformed to the original space. Using the transformation loss, pseudo labels are generated and cleaned using a transformer label cleaner. The proposed transformer-based pseudo-label generator and cleaner modules mutually train each other iteratively in an unsupervised manner. A discriminative learning mechanism is introduced to improve normal versus cancerous instance labeling. In addition to the unsupervised learning, we demonstrate the effectiveness of the proposed framework for weakly supervised learning and cancer subtype classification as downstream analysis. Extensive experiments on four publicly available datasets show better performance of the proposed algorithm compared to the existing state-of-the-art methods. [Display omitted] • We propose a fully unsupervised mutual transformer learning algorithm for instance-level predictions for WSI classification. To the best of our knowledge, it is the first rigorous attempt to tackle the WSI classification problem in a fully unsupervised manner. • The proposed architecture consists of two modules including a transformer pseudo-label generator and transformer label cleaner, with both modules learning mutually from each other and improving the performance for instance-level classification. • The transformer pseudo-label generator is based on the novel idea of learning a latent space via discriminative learning such that disease-negative instances can be inverse transformed with small errors while disease-positive instances observe large transformation errors. • We perform rigorous experimental evaluations on four different WSI classification datasets. Cancer subtype classification is also evaluated as a downstream analysis task with weak supervision. Our results demonstrate the excellent performance of the proposed algorithm compared to several SOTA methods. [ABSTRACT FROM AUTHOR]

Traditional cancer diagnosis has been aided by the application of nanoparticles (NPs), which have made the process easier and faster. NPs possess exceptional properties such as a larger surface area, higher volume proportion, and better targeting capabilities. Additionally, their low toxic effect on healthy cells enhances their bioavailability and t-half by allowing them to functionally penetrate the fenestration of epithelium and tissues. These particles have attracted attention in multidisciplinary areas, making them the most promising materials in many biomedical applications, especially in the treatment and diagnosis of various diseases. Today, many drugs are presented or coated with nanoparticles for the direct targeting of tumors or diseased organs without harming normal tissues/cells. Many types of nanoparticles, such as metallic, magnetic, polymeric, metal oxide, quantum dots, graphene, fullerene, liposomes, carbon nanotubes, and dendrimers, have potential applications in cancer treatment and diagnosis. In many studies, nanoparticles have been reported to show intrinsic anticancer activity due to their antioxidant action and cause an inhibitory effect on the growth of tumors. Moreover, nanoparticles can facilitate the controlled release of drugs and increase drug release efficiency with fewer side effects. Nanomaterials such as microbubbles are used as molecular imaging agents for ultrasound imaging. This review discusses the various types of nanoparticles that are commonly used in cancer diagnosis and treatment.

Simple Summary: Chemotherapy, radiotherapy and surgery are the primary therapies for cancer. Even with these current treatment modalities, the death rate for many cancers is still high. Thus, there is still an urgent need for new therapeutic approaches which are safer and more effective. Cancer biomarker targeting is a promising strategy for cancer treatment. Cancer cells are distinguished from normal cells by their unregulated differentiation and over or under-expression of certain biomarkers or alteration of genetic material. In this review, we discuss phosphatidylserine biomarker-targeted therapy and imaging modalities in pre-clinical and clinical studies. We also appraise chemotherapy, radiotherapy and electric field-enhanced biomarker-driven therapeutic approaches. Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human–mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies. Recent studies have demonstrated that upregulation of surface PS exposure by chemodrugs, radiation, and external electric fields can be used as a novel approach to sensitize cancer cells to PS-targeting anticancer drugs. The objectives of this review are to provide an overview of a unique dual-role of PS as a biomarker/target for cancer imaging and therapy, and to discuss PS-based anticancer strategies that are currently under active development. [ABSTRACT FROM AUTHOR]

Simple Summary: Inorganic nanocrystals such as gold, iron oxide and semiconductor nanocrystals have intrinsic optical or magnetic properties that make them very promising for cancer detection, imaging and therapy. The surface ligands of these nanoparticles play a critical role in their application and control the nanoparticle interaction with biomolecules and cells. The complex nano-bio interface is, for this reason, gaining increasing attention, and many studies are devoted to either propose new surface chemistries or characterize their impact on nanoparticle imaging and/or therapeutic efficiency. This review presents a general perspective on the design of nanoparticle surface chemistry. Inorganic nanocrystals, such as gold, iron oxide and semiconductor quantum dots, offer promising prospects for cancer diagnostics, imaging and therapy, due to their specific plasmonic, magnetic or fluorescent properties. The organic coating, or surface ligands, of these nanoparticles ensures their colloidal stability in complex biological fluids and enables their functionalization with targeting functions. It also controls the interactions of the nanoparticle with biomolecules in their environment. It therefore plays a crucial role in determining nanoparticle biodistribution and, ultimately, the imaging or therapeutic efficiency. This review summarizes the various strategies used to develop optimal surface chemistries for the in vivo preclinical and clinical application of inorganic nanocrystals. It discusses the current understanding of the influence of the nanoparticle surface chemistry on its colloidal stability, interaction with proteins, biodistribution and tumor uptake, and the requirements to develop an optimal surface chemistry. [ABSTRACT FROM AUTHOR]

Hypoxia is common in solid tumors and creates an immunosuppressive environment that leads to resistance to immunotherapy, such as an anti-programmed death receptor-1 (PD-1) therapy. It has been suggested that anti-PD-1 therapy may reduce tumor hypoxia by remodeling the tumor vasculature; however, it is unclear how anti-PD-1 therapy reduces hypoxia over time. Therefore, we investigated the relationship between hypoxia and immune activation by anti-PD-1 therapy in murine cancer models. Anti-PD-1 antibody was injected to CT26- and MC38-tumor-bearing mice on days 0 and 5. Tumor hypoxia was non-invasively evaluated using positron emission tomography (PET) with [18F]fluoromisonidazole ([18F]FMISO) on days 3 and 7. Histological analysis was conducted to investigate the infiltration of immune cells in [18F]FMISO-accumulated hypoxic area. In addition, the immune cell population in tumors and the percentages of cancer and immune cells under hypoxic conditions were analyzed at single-cell level using flow cytometry. Flow cytometric analysis of CT26 tumors on day 3 showed that anti-PD-1 therapy reduced hypoxia without inhibition of tumor growth. In addition, the infiltration of CD8+ T cells was increased in treated tumors. In contrast to CT26 tumors, the percentage of hypoxic cells in MC38 tumors did not change on days 3 and 7, and there was minimal immune activation induced by anti-PD-1 antibody. Changes in hypoxia in CT26 tumors were not detected by [18F]FMISO-PET, but autoradiogram showed that [18F]FMISO accumulated in immunosuppressed areas, where the infiltration of immune cells was relatively low. Reduction of hypoxia was induced in CT26 tumor, in which adequate immune response to anti-PD-1 therapy was exhibited, at an early time point before suppression of tumor growth. Our findings suggest that anti-PD-1 therapy can create a tumor microenvironment that facilitates immune activation by reducing hypoxia. [Display omitted] [ABSTRACT FROM AUTHOR]

Dynamic PET (dPET) imaging can be utilized to perform kinetic modelling of various physiologic processes, which are exploited by the constantly expanding range of targeted radiopharmaceuticals. To date, dPET remains primarily in the research realm due to a number of technical challenges, not least of which is addressing partial volume effects (PVE) in the input function. We propose a series of equations for the correction of PVE in the input function and present the results of a validation study, based on a purpose built phantom. 18F-dPET experiments were performed using the phantom on a set of flow tubes representing large arteries, such as the aorta (1" 2.54 cm ID), down to smaller vessels, such as the iliac arteries and veins (1/4" 0.635 cm ID). When applied to the dPET experimental images, the PVE correction equations were able to successfully correct the image-derived input functions by as much as 59 ± 35% in the presence of background, which resulted in image-derived area under the curve (AUC) values within 8 ± 9% of ground truth AUC. The peak heights were similarly well corrected to within 9 ± 10% of the scaled DCE-CT curves. The same equations were then successfully applied to correct patient input functions in the aorta and internal iliac artery/vein. These straightforward algorithms can be applied to dPET images from any PET-CT scanner to restore the input function back to a more clinically representative value, without the need for high-end Time of Flight systems or Point Spread Function correction algorithms. [ABSTRACT FROM AUTHOR]

Manganese has recently been exploited for cancer immunotherapy, fenton-like reaction-mediated chemo-dynamic therapy, and magnetic resonance imaging. The integration of multiple roles of manganese into one platform is of great significance for cancer theranostics and tumor inhibition. Here, we designed a multifunctional nanoplatform based on manganese, which consisted of a manganese-containing inner core and a phospholipid bilayer shell co-loaded with glucose oxidase (GOx), paclitaxel (PTX), and a NIR fluorescent dye (NanoMn-GOx-PTX). In a pH-dependent manner, the nanoplatform released manganese ions and payloads inside the tumor cells. In vitro characterization and cellular experiments indicated that NanoMn-GOx-PTX could catalyze the conversion of glucose into reactive oxygen species (ROS) through a cascade Fenton-like reaction as well as release free PTX. The consumption of glucose, ROS production, and the chemotherapeutic effect of PTX contributed to the superior cytotoxicity and apoptosis of 4T1 cancer cells. Moreover, NanoMn-GOx-PTX effectively induced the production of large amounts of type I interferon and pro-inflammatory cytokines in vivo, activating the innate immune response. Through the synergistic functions of the above components, NanoMn-GOx-PTX exerted the strongest anti-tumor effect in 4T1 tumor-bearing models. Therefore, the manganese-based nanoplatform could serve as a promising theranostic tool for breast cancer therapy. 1) This nanoplatform can be used as a universal tool for delivering proteins and anticancer drugs into cells; 2) The PEG-modified phospholipid bilayer shell plays a significant role in retarding the release of overloaded manganese ions and drugs in a pH-sensitive manner; 3) The released Mn2+ has the ability to enhance T1 contrast in magnetic resonance imaging; 4) The released Mn2+ can function as nanoadjuvants to activate the cGAS-STING pathway and effectively induce the natural immune response;5) The overloaded manganese ions are combined with glucose oxidase to form a cascade reaction system, indirectly converting glucose into ROS to induce oxidative damage of tumor tissue. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Being able to detect and image tumors is extremely important for proper diagnosis and treatment. The most sensitive technique, positron emission tomography (PET), is widely applied for such a purpose. Additionally, fluorescence imaging can be used to visually see the margins between healthy and cancerous tissue during surgery. These two techniques can be combined to optimize patient outcomes by ensuring maximum tumor removal. This review will discuss the work that has been done recently to combine these two imaging capabilities into one imaging agent. Dual probes that possess positron emission tomography (PET) and fluorescence imaging (FI) capabilities are precision medicine tools that can be used to improve patient care and outcomes. Detecting tumor lesions using PET, an extremely sensitive technique, coupled with fluorescence-guided surgical resection of said tumor lesions can maximize the removal of cancerous tissue. The development of novel molecular probes is important for targeting different biomarkers as every individual case of cancer has different characteristics. This short review will discuss some aspects of dual PET/FI probes and explore the recently reported examples. [ABSTRACT FROM AUTHOR]

Interstitial fluid pressure, interstitial fluid velocity and related parameters are of great clinical significance for cancer diagnosis, prognosis and treatment. A limited number of non-invasive techniques can be used to estimate these mechanopathological parameters in cancers in vivo. In this study, we designed and tested new ultrasound poroelastography methods capable of estimating the magnitude and spatial distribution of fluid pressure, fluid velocity and fluid flow inside tumors under external compression. We theoretically proved that fluid pressure, velocity and flow estimated using poroelastography from a tumor under creep compression are directly related to the underlying interstitial fluid pressure, interstitial fluid velocity and fluid flow, respectively, differing only in peak values. Furthermore, by knowledge of the spatial distribution of the fluid pressure estimated using poroelastography, it is possible to derive: the parameter $\alpha $ , which quantifies the spatial distribution of the interstitial fluid pressure, the vascular permeability to interstitial permeability ratio and the peak interstitial fluid pressure to effective vascular pressure ratio in the tumor. Our techniques were validated using finite element and ultrasound simulations for a variety of simulated phantoms. Excellent qualitative agreement was found between the fluid pressure and velocity obtained using the finite element models and the corresponding fluid pressure and fluid velocity obtained using the proposed models. The estimated parameter $\alpha $ was found to differ from the corresponding theoretical value by less than 10%. Experiments on a human breast cancer animal model were used as proof-of-principle of the feasibility of the proposed methods in vivo.

Cachexia is a significant contributor to cancer mortality as it is responsible for up to 30% of cancer deaths. Magnetic resonance imaging offers a noninvasive approach to detect features of cachexia. T1-weighted images of cachectic patients have a “pseudo fat-saturated” appearance secondary to disappearance of subcutaneous and fascial fat throughout the body, as well as fat in the bone marrow. Orbital fat remains preserved until late disease. We present 2 cases with these classic imaging findings of cancer cachexia in the subcutaneous tissues of the head, neck, and spine. This imaging phenomenon is often misinterpreted by radiologists and may lead to delayed diagnosis or unnecessary repeat imaging.

The CHAIMELEON project aims to set up a pan-European repository of health imaging data, tools and methodologies, with the ambition to set a standard and provide resources for future AI experimentation for cancer management. The project is a 4 year long, EU-funded project tackling some of the most ambitious research in the fields of biomedical imaging, artificial intelligence and cancer treatment, addressing the four types of cancer that currently have the highest prevalence worldwide: lung, breast, prostate and colorectal. To allow this, clinical partners and external collaborators will populate the repository with multimodality (MR, CT, PET/CT) imaging and related clinical data. Subsequently, AI developers will enable a multimodal analytical data engine facilitating the interpretation, extraction and exploitation of the information stored at the repository. The development and implementation of AI-powered pipelines will enable advancement towards automating data deidentification, curation, annotation, integrity securing and image harmonization. By the end of the project, the usability and performance of the repository as a tool fostering AI experimentation will be technically validated, including a validation subphase by world-class European AI developers, participating in Open Challenges to the AI Community. Upon successful validation of the repository, a set of selected AI tools will undergo early in-silico validation in observational clinical studies coordinated by leading experts in the partner hospitals. Tool performance will be assessed, including external independent validation on hallmark clinical decisions in response to some of the currently most important clinical end points in cancer. The project brings together a consortium of 18 European partners including hospitals, universities, R&D centers and private research companies, constituting an ecosystem of infrastructures, biobanks, AI /in-silico experimentation and cloud computing technologies in oncology. [ABSTRACT FROM AUTHOR]

[Display omitted] Dysregulated energy metabolism has recently been recognized as an emerging hallmark of cancer. Tumor cells, which are characterized by abnormal glycolysis, exhibit a lower extracellular pH (6.5–7.0) than normal tissues (7.2–7.4), providing a promising target for tumor-specific imaging and therapy. However, most pH-sensitive materials are unable to distinguish such a subtle pH difference owing to their wide and continuous pH-responsive range. In this study, we developed an efficient strategy for the fabrication of a tumor metabolic acidity-activatable calcium phosphate (CaP) fluorescent probe (termed MACaP9). Unlike traditional CaP-based biomedical nanomaterials, which only work within more acidic organelles, such as endosomes and lysosomes (pH 4.0–6.0), MACaP9 could not only specifically respond to the tumor extra-cellular pH but also rapidly convert pH variations into a distinct fluorescence signal to visually distinguish tumor from normal tissues. The superior sensitivity and specificity of MACaP9 enabled high-contrast visualization of a broad range of tumors, as well as small tumor lesions. [ABSTRACT FROM AUTHOR]

Localizing the site of tumor origin for patients with lymphoid tumor is fairly difficult before the definitive detection of the primary tumor, which causes redundant imaging examinations and medical costs. To circumvent this obstacle, the emergence of the world's first total-body positron emission tomography/computed tomography (PET/CT) provides a transformative platform for simultaneously static and dynamic human molecular imaging. Here, we reported a case of lymph node metastasis from an unknown primary tumor, and the primary tumor was detected with the aid of the total-body PET/CT scanner. This patient with right neck mass was subjected to static and dynamic PET scan, as the static PET imaging found irregular thickening of the upper rectal wall and the dynamic PET imaging recognized the associations between the lymph metastasis and the rectal tumor lesions. The diagnosis by the total-body PET/CT was confirmed by pathological examination. [ABSTRACT FROM AUTHOR]

Cancer has been a serious threat to human health. Among drug delivery carriers, protein nanoparticles are unique because of their mild and environmentally friendly preparation methods. They also inherit desired characteristics from natural proteins, such as biocompatibility and biodegradability. Therefore, they have solved some problems inherent to inorganic nanocarriers such as poor biocompatibility. Also, the surface groups and cavity of protein nanoparticles allow for easy surface modification and drug loading. Besides, protein nanoparticles can be combined with inorganic nanoparticles or contrast agents to form multifunctional theranostic platforms. This review introduces representative protein nanoparticles applicable in cancer theranostics, including virus-like particles, albumin nanoparticles, silk protein nanoparticles, and ferritin nanoparticles. It also describes the common methods for preparing them. It then critically analyzes the use of a variety of protein nanoparticles in improved cancer imaging and therapy. [ABSTRACT FROM AUTHOR]

Purpose: (S)-4-(3-18F-Fluoropropyl)-ʟ-Glutamic Acid ([18F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system xC-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [18F]FSPG production are required. Here, we report a cassette-based method to produce [18F]FSPG at high radioactivity concentrations from low amounts of starting activity. Procedures: An automated synthesis and purification of [18F]FSPG was developed using the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [18F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [18F]FSPG in phosphate-buffered saline. Subsequently, the [18F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer. Results: The optimized protocol produced [18F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led to significant improvements in radiotracer concentration from <10 MBq/ml to >100 MBq/ml. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [18F]Fluoride. Conclusions: We have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [18F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation. [ABSTRACT FROM AUTHOR]

Purpose: To analyze emergency department (ED) computerized tomography (CT) utilization in cancer patients with coronavirus disease 2019 (COVID-19). Methods: A retrospective chart review was performed to identify cancer patients who received COVID-19 diagnosis within the single healthcare system and presented to the ED within 30 days of COVID-19 positive date between May 1 and December 31, 2020. Results: In our 61 patients, the mean age was 72.5 years old, with 34% of patients (n = 21) on active cancer therapy and 66% (n = 40) on surveillance only. Most patients (n = 53) received their COVID-19 diagnosis within the ED, with 8 patients diagnosed prior to initial ED visit. The most common CT studies ordered within the ED were CT chest (n = 25), CT abdomen/pelvis (A/P) (n = 20), CT head (n = 8), and CT chest/abdomen/pelvis (C/A/P) (n = 7). COVID-19 findings were present on 33 scans, findings of worsening malignancy on 12 scans, and non-COVID non-cancer findings on 9 scans. Significant differences in CT severity score (p = 0.0001), indication for hospitalization (p = 0.026), length of hospitalization (p = 0.004), interventions (remdesivir, mechanical ventilation, and vasopressor support) while hospitalized (p < 0.05), and mortality (p = 0.042) were found between the prior diagnosis and ED diagnosis groups. No such differences were found between the active treatment and surveillance groups. Conclusion: ED CT imaging findings in patients with cancer and COVID-19 are predominantly related to COVID-19 infection, rather than cancer history or anti-cancer therapy status. [ABSTRACT FROM AUTHOR]

Due to the rarity of primary bone tumors, precise radiologic diagnosis often requires an experienced musculoskeletal radiologist. In order to make the diagnosis more precise and to prevent the overlooking of potentially dangerous conditions, artificial intelligence has been continuously incorporated into medical practice in recent decades. This paper reviews some of the most promising systems developed, including those for diagnosis of primary and secondary bone tumors, breast, lung and colon neoplasms.

Abstract Background To evaluate the inter- and intrareader agreement and reproducibility of the NI-RADS scoring system and lexicon with contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI). Methods This retrospective study included 97 CECT and CEMRI scans from 58 treated cases of head and neck squamous cell carcinoma (HNSCC) after the exclusion of head and neck cancers (HNCs) other than SCC and noncontrast and poor quality CT and MRI scans, with a total of 111 primary targets and 124 lymph node (LN) targets. Two experienced readers independently scored the likelihood of residual/recurrence for these targets based on the NI-RADS criteria and filled in report templates for NI-RADS lexicon diagnostic features. Inter- and intraobserver reproducibility was assessed with Cohen’s kappa, and the percent agreement was calculated. Results Almost perfect interreader agreement was found for the final NI-RADS category of the primary lesions and LNs, with K = 0.808 and 0.806, respectively. Better agreement was found for CT than for MRI (K = 0.843 and 0.77, respectively, P value 0.001). There was almost perfect agreement for excluding tissue enhancement (K = 0.826, 95% CI = 0.658–0.993, P value 0.001), with a percent agreement of 96.4%, and substantial agreement for discrete nodular and diffuse mucosal enhancement (K = 0.826, 95% CI = 0.658–0.993, P value 0.001), with a percent agreement of 96.4%. There was fair agreement for focal mucosal nonmass and deep ill-defined enhancement. The intrareader agreement was almost perfect for most of the rated features (K ranging from 0.802 to 1), with the exception of enlarging discrete nodule/mass and focal mucosal nonmass-like enhancement, which had substantial intraobserver agreement (K ranging from 0.768 to 0.786). Conclusion The individual features of NI-RADS show variable degrees of confidence; however, the overall NI-RADS category was not significantly affected.