Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chlorotoxin-A Multimodal Imaging Platform for Targeting Glioma Tumors.

ABSTRACT: Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus. CTX alters physiology in numerous ways. It interacts with voltage gated chloride channels, Annexin-2, and matrix metalloproteinase-2 (MMP-2). CTX-based bioconjugates have been widely subjected to phase I/II clinical trials and have shown substantial promise. Many studies have demonstrated that CTX preferentially binds to neuroectodermal tumors, such as glioblastoma, without cross-reactivity to normal brain cells. With its ability to penetrate the blood-brain-barrier (BBB) and its tyrosine residue allows covalent conjugation with functional moieties, CTX is an attractive platform to explore development of diagnostic and therapeutic agents for gliomas. In this review, we outline CTX structure and its molecular targets, summarize molecular variations of CTX developed for glioma imaging, and discuss future trends and perspectives for CTX conjugates as a theranostic agent.

SUBMITTER: Cohen G

PROVIDER: S-EPMC6316809 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Chlorotoxin-A Multimodal Imaging Platform for Targeting Glioma Tumors.

Cohen Gadi G Burks Scott R SR Frank Joseph A JA

Toxins 20181126 12

Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion <i>Leiurus quinquestriatus</i>. CTX alters physiology in numerous ways. It interacts with voltage gated chloride channels, Annexin-2, and matrix metalloproteinase-2 (MMP-2). CTX-based bioconjugates have been widely subjected to phase I/II clinical trials and have shown substantial promise. Many studies have demonstrated that CTX preferentially binds to neuroectodermal tumors, such as glioblas ...[more]

PMID: 30486274

Similar Datasets

Chlorotoxin peptide-functionalized polyethylenimine-entrapped gold nanoparticles for glioma SPECT/CT imaging and radionuclide therapy.

Project description:BACKGROUND:Malignant glioma is the most common and deadliest brain cancer due to the obstacle from indistinct tumor margins for surgical excision and blood brain barrier (BBB) for chemotherapy. Here, we designed and prepared multifunctional polyethylenimine-entrapped gold nanoparticles (Au PENPs) for targeted SPECT/CT imaging and radionuclide therapy of glioma. RESULTS:Polyethylenimine was selected as a template for sequential modification with polyethylene glycol (PEG), glioma-specific peptide (chlorotoxin, CTX) and 3-(4-hydroxyphenyl)propionic acid-OSu (HPAO), and were then used to entrap gold nanoparticles (Au NPs). After 131I radiolabeling via HPAO, the 131I-labeded CTX-functionalized Au PENPs as a multifunctional glioma-targeting nanoprobe were generated. Before 131I radiolabeling, the CTX-functionalized Au PENPs exhibited a uniform size distribution, favorable X-ray attenuation property, desired water solubility, and cytocompatibility in the given Au concentration range. The 131I-labeled CTX-functionalized Au PENPs showed high radiochemical purity and stability, and could be used as a nanoprobe for the targeted SPECT/CT imaging and radionuclide therapy of glioma cells in vitro and in vivo in a subcutaneous tumor model. Owing to the unique biological properties of CTX, the developed nanoprobe was able to cross the BBB and specifically target glioma cells in a rat intracranial glioma model. CONCLUSIONS:Our results indicated that the formed nanosystem had the significant potential to be applied for glioma targeted diagnosis and therapy.

| S-EPMC6380014 | biostudies-literature

Nanodiscs as a Modular Platform for Multimodal MR-Optical Imaging.

Project description:Nanodiscs are monodisperse, self-assembled discoidal particles that consist of a lipid bilayer encircled by membrane scaffold proteins (MSP). Nanodiscs have been used to solubilize membrane proteins for structural and functional studies and deliver therapeutic phospholipids. Herein, we report on tetramethylrhodamine (TMR) tagged nanodiscs that solubilize lipophilic MR contrast agents for generation of multimodal nanoparticles for cellular imaging. We incorporate both multimeric and monomeric Gd(III)-based contrast agents into nanodiscs and show that particles containing the monomeric agent (ND2) label cells with high efficiency and generate significant image contrast at 7 T compared to nanodiscs containing the multimeric agent (ND1) and Prohance, a clinically approved contrast agent.

| S-EPMC4486023 | biostudies-literature

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

Project description:A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

| S-EPMC4763738 | biostudies-other

Radiosynthesis and Preliminary Biological Evaluation of <sup>18</sup>F-Fluoropropionyl-Chlorotoxin as a Potential PET Tracer for Glioma Imaging.

Project description:PurposesChlorotoxin can specifically bind to matrix metalloproteinase 2 (MMP-2), which are overexpressed in the glioma. In this work, radiosynthesis of [18F]-fluoropropionyl-chlorotoxin ([18F]-FP-chlorotoxin) as a novel PET tracer was investigated, and biodistribution in vivo and PET imaging were performed in the C6 glioma model.Procedures[18F]-FP-chlorotoxin was prepared from the reaction of chlorotoxin with [18F]-NFB (4-nitrophenyl 2-[18F]-fluoropropionate), which was synthesized from multistep reactions. Biodistribution was determined in 20 normal Kunming mice. Small-animal PET imaging with [18F]-FP-chlorotoxin was performed on the same rats bearing orthotopic C6 glioma at different time points (60 min, 90 min, and 120 min) after injection and compared with 2-deoxy-2-[18F] fluoro-D-glucose ([18F]-FDG).Results[18F]-FP-Chlorotoxin was successfully synthesized in the radiochemical yield of 41% and the radiochemical purity of more than 98%. Among all the organs, the brain had the lowest and stable uptake of [18F]-FP-chlorotoxin, while the kidney showed the highest uptake. Compared with [18F]-FDG, a low uptake of [18F]-FP-chlorotoxin was detected in normal brain parenchyma and a high accumulation of [18F]-FP-chlorotoxin was found in the gliomas tissue. The glioma to normal brain uptake ratio of [18F]-FP-chlorotoxin was higher than that of [18F]-FDG. Furthermore, the uptake of [18F]-FP-chlorotoxin at 90 min after injection was better than that at 60 min after injection.ConclusionsCompared with [18F]-FDG, [18F]-FP-chlorotoxin has a low and stable uptake in normal brain parenchyma. [18F]-FP-Chlorotoxin seems to be a potential PET tracer with a good performance in diagnosis of the glioma.

| S-EPMC6317094 | biostudies-literature

Glioma Cell Migration Dynamics in Brain Tissue Assessed by Multimodal Optical Imaging.

Project description:Glioblastoma is a primary malignant brain tumor characterized by highly infiltrative glioma cells. Vasculature and white matter tracts are considered to be the preferred and fastest routes for glioma invasion through brain tissue. In this study, we systematically quantified the routes and motility of the U251 human glioblastoma cell line in mouse brain slices by multimodal imaging. Specifically, we used polarization-sensitive optical coherence tomography to delineate nerve fiber tracts while confocal fluorescence microscopy was used to image cell migration and brain vasculature. Somewhat surprisingly, we found that in mouse brain slices, U251 glioma cells do not follow white matter tracts but rather preferentially migrate along vasculature in both gray and white matter. In addition, U251 cell motility is ∼2-fold higher in gray matter than in white matter (91 vs. 43 μm2/h), with a substantial fraction (44%) of cells in both regions invading without close association with vasculature. Interestingly, within both regions, the rates of migration for the perivascular and televascular routes of invasion were indistinguishable. Furthermore, by imaging of local vasculature deformation dynamics during cell migration, we found that U251 cells are capable of exerting traction forces that locally pull on their environment, suggesting the applicability of a "motor-clutch"-based model for migration in vivo. Overall, by quantitatively analyzing the migration dynamics along the diverse pathways followed by invading U251 glioma cells as observed by our multimodal imaging approach, our studies suggest that effective antiinvasive strategies will need to simultaneously limit parallel routes of both perivascular and televascular invasion through both gray and white matter.

| S-EPMC6818150 | biostudies-literature

Effects of electrode surface modification with chlorotoxin on patterning single glioma cells.

Project description:A microchip patterned with arrays of single cancer cells can be an effective platform for the study of tumor biology, medical diagnostics, and drug screening. However, patterning and retaining viable single cancer cells on defined sites of the microarray can be challenging. In this study we used a tumor cell-specific peptide, chlorotoxin (CTX), to mediate glioma cell adhesion on arrays of gold microelectrodes and investigated the effects of three surface modification schemes for conjugation of CTX to the microelectrodes on single cell patterning, which include physical adsorption, covalent bonding mediated by N-hydroxysuccinimide (NHS), and covalent bonding via crosslinking succinimidyl iodoacetate and Traut's (SIA-Traut) reagents. The CTX immobilization to microelectrodes was confirmed by high-resolution X-ray photoelectron spectroscopy. Physically adsorbed CTX showed better support for cell adhesion and is more effective in confining adhered cells on the electrodes than covalently-bound CTX. Furthermore, cell adhesion and spreading on microelectrodes were quantified in real-time by impedance measurements, which revealed an impedance signal from physically adsorbed CTX electrodes four times greater than the signal from covalently-bound CTX electrodes.

| S-EPMC3205118 | biostudies-literature

Platinum(IV)-chlorotoxin (CTX) conjugates for targeting cancer cells.

Project description:Cisplatin is one of the most widely used anticancer drugs. Its side effects, however, have motivated researchers to search for equally effective analogs that are better tolerated. Selectively targeting cancer tissue is one promising strategy. For this purpose, a platinum(IV) complex was conjugated to the cancer-targeting peptide chlorotoxin (CTX, TM601) in order to deliver cisplatin selectively to cancer cells. The 1:1 Pt-CTX conjugate was characterized by mass spectrometry and gel electrophoresis. Like most platinum(IV) derivatives, the cytotoxicity of the conjugate was lower in cell culture than that of cisplatin, but greater than those of its Pt(IV) precursor and CTX in several cancer cell lines.

| S-EPMC3350571 | biostudies-literature

PET imaging and pharmacological therapy targeting carbonic anhydrase-IX high-expressing tumors using US2 platform based on bivalent ureidosulfonamide.

Project description:Carbonic anhydrase-IX (CA-IX) is attracting much attention as a target molecule for cancer treatment since high expression of CA-IX can lead to a poor prognosis of patients. We previously reported low-molecular-weight 111In/90Y complexes with a bivalent ureidosulfonamide scaffold ([111In/90Y]In/Y-US2) as cancer radiotheranostic agents for single photon emission computed tomography and radionuclide-based therapy targeting CA-IX. Here, we applied the US2 platform to positron emission tomography (PET) imaging and pharmacological therapy targeting CA-IX high-expressing tumors by introducing 68Ga and natIn, respectively. In an in vitro cell binding assay, [67Ga]Ga-US2, an alternative complex of [68Ga]Ga-US2 with a longer half-life, markedly bound to CA-IX high-expressing (HT-29) cells compared with low-expressing (MDA-MB-231) cells. In a biodistribution study with HT-29 and MDA-MB-231 tumor-bearing mice, [67Ga]Ga-US2 showed accumulation in the HT-29 tumor (3.81% injected dose/g at 60 min postinjection) and clearance from the blood pool with time. PET with [68Ga]Ga-US2 clearly visualized the HT-29 tumor in model mice at 60 min postinjection. In addition, the administration of [natIn]In-US2 to HT-29 tumor-bearing mice led to tumor growth delay and prolonged mouse survival, while no critical toxicity was observed. These results indicate that [68Ga]Ga-US2 and [natIn]In-US2 may be useful imaging and therapeutic agents targeting CA-IX, respectively, and that US2 may serve as an effective cancer theranostic platform utilizing CA-IX.

| S-EPMC7725290 | biostudies-literature

Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning.

Project description:Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise difficult-to-assess low-grade glioma. We validate our findings against the gold standard histology and use attenuation and fluorescence intensity measures to differentiate between tumor core, infiltrative zone and adjacent brain tissue. Using large field-of-view scans acquired by a near-infrared swept-source optical coherence tomography setup, we provide initial assessments of tumor heterogeneity. Finally, we use cross-sectional OCM images to train a convolutional neural network that discriminates tumor from non-tumor tissue with an accuracy of 97%. Collectively, the present hybrid approach offers potential to translate into an in vivo imaging setup for substantially improved intraoperative guidance of brain tumor surgeries.

| S-EPMC7408054 | biostudies-literature

A Multimodal Platform for Simultaneous T-Cell Imaging, Defined Activation, and Mechanobiological Characterization.

Project description:T-cell antigen recognition is accompanied by extensive morphological rearrangements of the contact zone between the T-cell and the antigen-presenting cell (APC). This process involves binding of the T-cell receptor (TCR) complex to antigenic peptides presented via MHC on the APC surface, the interaction of costimulatory and adhesion proteins, remodeling of the actin cytoskeleton, and the initiation of downstream signaling processes such as the release of intracellular calcium. However, multiparametric time-resolved analysis of these processes is hampered by the difficulty in recording the different readout modalities at high quality in parallel. In this study, we present a platform for simultaneous quantification of TCR distribution via total internal reflection fluorescence microscopy, of intracellular calcium levels, and of T-cell-exerted forces via atomic force microscopy (AFM). In our method, AFM cantilevers were used to bring single T-cells into contact with the activating surface. We designed the platform specifically to enable the study of T-cell triggering via functionalized fluid-supported lipid bilayers, which represent a widely accepted model system to stimulate T-cells in an antigen-specific manner. In this paper, we showcase the possibilities of this platform using primary transgenic T-cells triggered specifically via their cognate antigen presented by MHCII.

| S-EPMC7910839 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data