Tumor-specific Imaging Research Articles

Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases.

In epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide surgeons to detect metastases otherwise not visible to the naked eye. Previously, we identified 29% more metastatic lesions during cytoreductive surgery using OTL-38, a fluorescent tracer targeting folate receptor-α (FRα). Unfortunately, eleven out of thirteen fluorescent lymph nodes were tumor negative. The current study evaluates the suitability of five biomarkers (EGFR, VEGF-A, L1CAM, integrin αvβ6 and EpCAM) as alternative targets for molecular imaging of EOC metastases and included FRα as a reference. Immunohistochemistry was performed on paraffin-embedded tissue sections of primary ovarian tumors, omental, peritoneal and lymph node metastases from 84 EOC patients. Tumor-negative tissue specimens from these patients were included as controls. EGFR, VEGF-A and L1CAM were highly expressed in tumor-negative tissue, whereas αvβ6 showed heterogeneous expression in metastases. The expression of EpCAM was most comparable to FRα in metastatic lesions and completely absent in the lymph nodes that were false-positively illuminated with OTL-38 in our previous study. Hence, EpCAM seems to be a promising novel target for intraoperative imaging and may contribute to a more reliable detection of true metastatic EOC lesions.

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo.

In Situ 3D-to-2D Transformation of Manganese-Based Layered Silicates for Tumor-Specific T1-Weighted Magnetic Resonance Imaging with High Signal-to-Noise and Excretability.

Recently, Mn(II)-based T1-weighted magnetic resonance imaging (MRI) contrast agents (CAs) have been explored widely for cancer diagnosis. However, the "always-on" properties and poor excretability of the conventional Mn(II)-based CAs leads to high background signals and unsatisfactory clearance from the body. Here, we report an "in situ three-dimensional to two-dimensional (3D-to-2D) transformation" method to prepare novel excretable 2D manganese-based layered silicates (Mn-LSNs) with extremely high signal-to-noise for tumor-specific MR imaging for the first time. Our observations combined with density functional theory (DFT) calculations reveal that 3D metal (Mn, Fe, Co) oxide nanoparticles are initially formed from the molecular precursor solution and then in situ transform into 2D metal (Mn, Fe, Co)-based layered silicates triggered by the addition of tetraethyl orthosilicate, which provides a time-saving and versatile way to prepare novel 2D silicate nanomaterials. The unique ion-exchangeable capacity and high host layer charge density endow Mn-LSNs with an "ON/OFF" pH/GSH stimuli-activatable T1 relaxivity with superb high signal-to-noise (640-, 1200-fold for slightly acidic and reductive changes, respectively). Further in vivo MR imaging reveals that Mn-LSNs exhibit a continuously rapid T1-MRI signal enhancement in tumor tissue and no visible signal enhancement in normal tissue, indicating an excellent tumor-specific imaging. In addition, Mn-LSNs exhibit a rapid excretion from the mouse body in 24 h and invisible organ toxicity, which could help to solve the critical intractable degradation issue of conventional inorganic CAs. Moreover, the tumor microenvironment (pH/GSH/H2O2) specific degradability of Mn-LSNs could help to improve the penetration depth of particles into the tumor parenchyma. Developing this novel Mn-LSNs contrast agent, together with the already demonstrated capacity of layered silicates for drug and gene delivery, provides opportunities for future cancer theranostics.

Tumour-specific fluorescence-guided surgery for pancreatic cancer using panitumumab-IRDye800CW: a phase 1 single-centre, open-label, single-arm, dose-escalation study

Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time. In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238. Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients. To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis. National Institutes of Health and the Netherlands Organization for Scientific Research.

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

BackgroundTo meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance.MethodsThe expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging.ResultsIn 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs.ConclusionsCOC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids.

Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery.

Engineered Near‐Infrared Fluorescent Protein Assemblies for Robust Bioimaging and Therapeutic Applications

Fluorescent proteins are investigated extensively as markers for the imaging of cells and tissues that are treated by gene transfection. However, limited transfection efficiency and lack of targeting restrict the clinical application of this method rooted in the challenging development of robust fluorescent proteins for in vivo bioimaging. To address this, a new type of near-infrared (NIR) fluorescent protein assemblies manufactured by genetic engineering is presented. Due to the formation of well-defined nanoparticles and spectral operation within the phototherapeutic window, the NIR protein aggregates allow stable and specific tumor imaging via simple exogenous injection. Importantly, in vivo tumor metastases are tracked and this overcomes the limitations of in vivo imaging that can only be implemented relying on the gene transfection of fluorescent proteins. Concomitantly, the efficient loading of hydrophobic drugs into the protein nanoparticles is demonstrated facilitating the therapy of tumors in a mouse model. It is believed that these theranostic NIR fluorescent protein assemblies, hence, show great potential for the in vivo detection and therapy of cancer.

Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor

Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded, naturally stable nanostructures, have been developed as the first ultrasonic biomolecular reporters which showed strong contrast enhancement. However, further development of tumor imaging with GVs is limited by the quick clearance of GVs by the reticuloendothelial system (RES). Here, we developed PEGylated HA-GVs (PH-GVs) for in-tumor molecular ultrasound imaging by integrating polyethylene glycol (PEG) and hyaluronic acid (HA) in GV shells. PH-GVs were observed to accumulate around CD44-positive cells (SCC7) but not be internalized by macrophage cell line RAW 264.7. Green fluorescence from PH-GVs was found around cell nuclei in the tumor site after 6 h and the signal was sustained over 48 h following tail injection, demonstrating PH-GVs’ ability to escape the clearance from the RES and to penetrate tumor vasculature through enhanced permeability and retention (EPR) effects. Further, PH-GVs produced strong ultrasound contrast in the tumor site in vivo, with no obvious side-effects detected following intravenous injection. Thus, we demonstrate the potential of PH-GVs as novel, nanosized and targeted UCAs for efficient and specific molecular tumor imaging, paving the way for the application of GVs in precise and personalized medicine.

Tumor microenvironment triggered biodegradation of inorganic nanoparticles for enhanced tumor theranostics.

Inorganic nanoparticles (NPs)-mediated tumor theranostics have attracted widespread attention due to their unique physicochemical properties, such as optical, electrical, magnetic, and thermal properties. In the past decade, great advancements have been made in inorganic NPs-associated drug delivery, multimodal tumor imaging, and tumor therapy. However, the potential toxicity of inorganic NPs due to their low biodegradability, background signals interference and treatment side effects limit their clinical application. Therefore, developing biodegradable and intelligent NPs is beneficial to avoid excessive metal ions deposition, specific tumor imaging and treatment. In this review, we summarize the recent advances in tumor microenvironment (TME)-triggered biodegradation of inorganic NPs accompanied by imaging signal amplification and the released ions-mediated tumor therapy. First, the feature characteristics of the TME are introduced, including mild acidity, hypoxia, overexpressed reactive oxygen species (ROS), glutathione (GSH), and enzymes et al.; then, the biodegradation of NPs in a TME-induced activation of imaging signals, such as magnetic resonance (MR) imaging and fluorescence imaging is described; furthermore, tumor therapies through “Fenton”, “Fenton-like” reactions, and interference of biological effects in cells is presented. Finally, the challenges and outlook for improving the degradation efficiency, imaging, specificity and efficiency of tumor imaging and treatment are discussed.

Cancer Nanotechnology in Medicine: A Promising Approach for Cancer Detection and Diagnosis

Despite extraordinary advances that have been made in cancer therapy, the number of cancer cases continue to surge, making it the leading cause of death across the world. As a result, early detection is one of the key aspects in the battle against the disease. Screening and early diagnosis play a pivotal role for effective treatment and to lower the cancer mortality rate. Cancer nanotechnology is a new branch in biology that provides a link between nanotechnology and clinical cancer research. Moreover, it also aims to integrate the advancements made in the manufacture of nanoscale devices with cellular and molecular components associated with cancer diagnosis and therapy. Understanding these new technologies is crucial to integrating these practices into clinical settings. This novel approach has facilitated the conjugation of nanoscale devices with agents such as tumor-specific li-gands, antibodies, and imaging probes. This review summarizes the advancements made in nanotechnology based approaches in diagnosing cancer. Coupling of nanoparticles with targeting molecules enables an efficient interaction between biological systems with extraordinary accuracy. The progress associated with nanoscale devices such as metal based nanomaterials, exosomes, magnetic nanoparticles, in addition to quantum dots and lab on chip devices with regard to diagnostic applications has been discussed. We summarize how nanoparticles take advantage of the tumor microenvironment for targeting cancer cells. Further, the review outlines the drawbacks, challenges, and future prospects associated with these techniques as effective strategies to replace current clinical trends.

Absolutely "off-on" fluorescent CD-based nanotheranostics for tumor intracellular real-time imaging and pH-triggered DOX delivery.

Carbon dots (CDs) have attracted intense attention in tumor nanotheranostics recently; however, those nanotheranostics exhibited similar fluorescence in both normal and tumor tissues, limiting their practical application. In the present work, absolutely "off-on" fluorescent CD-based nanotheranostics was designed for tumor intracellular real-time imaging and pH-triggered DOX delivery via both static quenching by the crosslinking of benzaldehyde-containing diblock copolymers and dynamic quenching because of the surrounding conjugated DOX molecules. The proposed PPEGMA42-b-PFPMA122-(CDs)-DOX nanotheranostics did not exhibit fluorescence in a normal physiological medium, while strong fluorescence recovery occurred in the tumor intracellular microenvironment due to pH-triggered disintegration, releasing the CDs and DOX. The pH-triggered DOX release and absolute "off-on" fluorescence make the proposed nanotheranostics promising for tumor-specific pH-triggered DOX delivery and imaging.

Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.

The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.

基于多角度光声介观成像方法的小动物肿瘤特异性成像

基于多角度光声介观成像方法的小动物肿瘤特异性成像

Development of Molecular Probes for Live Imaging of Cancer and Infectious Diseases

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are powerful molecular imaging methods for examining disease-related factors in the whole body using specific imaging probes. Recently, we tried to develop molecular imaging probes that specifically visualize pathological factors associated with cancers and infectious diseases. Although survivin is highly expressed in several cancers, its expression is undetectable in non-dividing tissues. Thus, we developed several small molecular imaging probes that target survivin. These ligands not only showed high affinity for survivin protein, but also showed consistent cellular accumulation with respect to survivin expression levels, thereby indicating the feasibility of their backbones as scaffolds for tumor-specific imaging agents that target survivin. Prion diseases are fatal neurodegenerative diseases characterized by the deposition of amyloid plaques containing abnormal prion protein aggregates (PrPSc). Thus, we developed flavonoids, acridines, and benzofurans as PrPSc-imaging probes. A styrylchromone derivative ([123I]SC-OMe) appears to be a particularly promising SPECT radioligand for monitoring prion deposit levels in living brains. Gallium-68 is a positron emitter in clinical PET applications that can be produced by a 68Ge/68Ga generator without a cyclotron. Notably, we developed new adsorbents for 68Ge by introducing N-methylglucamine groups into the Sephadex series to serve as a hydrophilic polymer matrix. We also demonstrated that generator-eluted 68Ga-citrate could be used for PET imaging of infectious mouse models. Our polysaccharide-based 68Ge/68Ga generators were shown to be prospectively cost-effective production systems for 68Ga radiopharmaceuticals. This Review describes the major findings of these three studies and the future prospect of these fields.

Pelvic lymph nodes and pathways of disease spread in male pelvic malignancies.

Accurate nodal staging for male urogenital malignancies has important implications for therapy and prognosis. Male pelvic malignancies, including prostatic, penile, testicular, and bladder cancer, typically metastasize to regional lymph nodes first which is reported by the N-stage. Spread beyond these groups to non-regional nodes is regarded as M-stage disease. In this review, we discuss the typical patterns of male pelvic lymphatic drainage and the tumor-specific regional nodal chains. The impact of tumor-specific imaging features and the implications of previous treatments on staging are discussed. While anatomic imaging, including CT and MRI, is the most widely employed imaging modality at present, newer functional imaging techniques have demonstrated promise in the accurate identification and characterization of nodal metastases.

Novel 18F-Labeled α-Methyl-Phenylalanine Derivative with High Tumor Accumulation and Ideal Pharmacokinetics for Tumor-Specific Imaging.

Positron emission tomography (PET) imaging with 18F-labeled α-methyl-substituted amino acids exerts significant influence on differential diagnosis of malignant tumors and tumor-like lesions. Exclusive uptake via L-type amino acid transporter 1 (LAT1), a tumor-specific transporter, accounts for their excellent tumor specificity and low background accumulation. However, further refinement and optimization in their tumor accumulation and pharmacokinetics are sorely needed. To address these issues, we newly designed 18F-labeled α-methyl-phenylalanine (18F-FAMP) regioisomers (2-, 3-, or 4-18F-FAMP) and stereoisomers (L- or D-form), and we comprehensively evaluated their potential as tumor-imaging agents. 18F-FAMPs were prepared from α-methyl phenylalanine by electrophilic radiofluorination and purified by reversed-phase HPLC. In biodistribution studies on normal mice, L-2-18F-FAMP and the three D-18F-FAMPs showed faster blood clearance and lower renal accumulation than L-3-18F-FAMP or L-4-18F-FAMP. In LS180 human colorectal cancer cell line xenograft mice, L-2-18F-FAMP exhibited significantly higher tumor accumulation than the D-18F-FAMPs or a clinically relevant tracer, L-3-18F-α-methyl-tyrosine (18F-FAMT) (p < 0.05). The renal accumulation levels of L-2-18F-FAMP were significantly lower than that of 18F-FAMT (p < 0.01). LAT-1 specificity of L-2-18F-FAMP was validated in the cellular uptake studies. The PET imaging with L-2-18F-FAMP clearly visualized the tumor as early as 1 h after injection, and the high tumor accumulation level was retained for 3 h. These findings suggest that L-2-18F-FAMP constitutes a potential PET tracer for tumor-specific imaging.

Novel near-infrared pH-sensitive cyanine-based fluorescent probes for intracellular pH monitoring

Real-time monitoring of intracellular pH fluctuation is of great significance for diagnosis of diseases and study of related physiological and pathological processes. A novel near-infrared (NIR) pH-activated parent probe 4 was developed, and further functionalized to afford probes 6 and 7. With the decrease of pH from 11 to 2, they all exhibited a new absorption peak and strong fluorescence emission in NIR region, accompanied by rapid solution color change from pink to pale green. Moreover, the probes’ fluorescence responses toward pH fluctuations were reversible and stable, and the pseudo-linear relationship between the fluorescence intensity and pH value can be used to detect pH value in 2.76–6.45 range quantitatively. Finally, probe 6 and 7 were successfully applied to monitor the fluctuation of intracellular pH by a fluorescence turn-on mode, and the imaging results confirmed their low cytotoxicity and satisfactory cell-membrane permeability, as well as their application prospect in disease diagnosis (such as tumor specific imaging) or assist in study of pH-related biological processes in wide acidic environment.

A pH-Sensitive Zwitterionic Iron Complex Probe with High Biocompatibility for Tumor-Specific Magnetic Resonance Imaging.

Accurate diagnosis of tumor characteristics, including its location and boundary, is of immense value to subsequent therapy. Activatable magnetic resonance imaging (MRI) contrast agents that respond to tumor-specific microenvironments, such as the redox state, pH, and enzyme activity, enable better mapping of tumor tissue. However, the practical application of most reported activatable agents is hampered by problems including potential toxicity, inefficient elimination, and slow activation. In this study, we developed a zwitterionic iron complex (Fe-ZDS) as a positive MRI contrast agent for tumor-specific imaging. Fe-ZDS could dissociate in weakly acidic solution rapidly, accompanied by clear longitudinal relaxivity (r1 ) enhancement, which enabled the complex to act as a pH-sensitive contrast agent for tumor-specific MR imaging. In vivo experiments showed that Fe-ZDS rapidly enhanced the tumor-to-normal contrast ratio by >40 %, which assisted in distinguishing the tumor boundary. Furthermore, Fe-ZDS circulated freely in the bloodstream and was excreted relatively safely via kidneys owing to its zwitterionic nature. Therefore, Fe-ZDS is an ideal candidate for a tumor-specific MRI contrast agent and holds considerable potential for clinical translation.

Nuclear Imaging of Glucose Metabolism: Beyond 18F-FDG.

Glucose homeostasis plays a key role in numerous fundamental aspects of life, and its dysregulation is associated with many important diseases such as cancer. The atypical glucose metabolic phenomenon, known as the Warburg effect, has been recognized as a hallmark of cancer and serves as a promising target for tumor specific imaging. At present, 2-deoxy-2-[18F]fluoro-glucose (18F-FDG)-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for this purpose. The powerful impact of 18F-FDG has prompted intensive research efforts into other glucose-based radiopharmaceuticals for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. Currently, glucose and its analogues have been labeled with various radionuclides such as 99mTc, 111In, 18F, 68Ga, and 64Cu and have been successfully investigated for tumor metabolic imaging in many preclinical studies. Moreover, 99mTc-ECDG has advanced into its early clinical trials and brings a new era of tumor imaging beyond 18F-FDG. In this review, preclinical and early clinical development of glucose-based radiopharmaceuticals for tumor metabolic imaging will be summarized.

Erythrocyte-derived vesicles for circulating tumor cell capture and specific tumor imaging.

The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.