Search results for: Mouse Anti-BrdU(A7) Monoclonal Antibody, Cy5 Conjugated
#31156310 // To Up
Synthesis and evaluation of Cu-radiolabeled NOTA-cetuximab (Cu-NOTA-C225) for immuno-PET imaging of EGFR expression.Epidermal growth factor receptor (EGFR) is overexpressed in a wide variety of solid tumors, serving as a well-characterized target for cancer imaging or therapy. In this study, we aimed to design and synthesize a radiotracer, Cu-NOTA-C225, targeting EGFR for tumor positron emission tomography (PET) imaging.
Xiaoxia Xu, Teli Liu, Fei Liu, Xiaoyi Guo, Lei Xia, Qing Xie, Nan Li, Haifeng Huang, Xianteng Yang, Yangchun Xin, Hua Zhu, Zhi Yang
2343 related Products with: Synthesis and evaluation of Cu-radiolabeled NOTA-cetuximab (Cu-NOTA-C225) for immuno-PET imaging of EGFR expression.5 G1 Set100ul10 mg 1 kit(s) 5 inhibitors 500 ml 50 50 mg
#29529089 2018/03/12 To Up
RAGE-specific single chain Fv for PET imaging of pancreatic cancer.Noninvasive detection of both early pancreatic neoplasia and metastases could enhance strategies to improve patient survival in this disease that is notorious for an extremely poor prognosis. There are almost no identifiable targets for non-invasive diagnosis by positron emission tomography (PET) for patients with pancreatic ductal adenocarcinoma (PDAC). Over-expression of the receptor for advanced glycation end products (RAGE) is found on the cell surface of both pre-neoplastic lesions and invasive PDAC. Here, a RAGE-specific single chain (scFv) was developed, specific for PET imaging in syngeneic mouse models of PDAC. An anti-RAGE scFv conjugated with a sulfo-Cy5 fluorescence molecule showed high affinity and selectivity for RAGE expressing pancreatic tumor cells and genetically engineered KRASG12D mouse models of PDAC. An in vivo biodistribution study was performed with the 64Cu-radiolabled scFv in a syngeneic murine pancreatic cancer model, demonstrating both the feasibility and potential of an anti-RAGE scFv for detection of PDAC. These studies hold great promise for translation into the clinic.
Hye-Yeong Kim, Xiaolei Wang, Rui Kang, Daolin Tang, Brian A Boone, Herbert J Zeh, Michael T Lotze, W Barry Edwards10 0.2 mg1 LITRE0.1 mg2 Pieces/Box
#29025987 2017/10/12 To Up
Preclinical Development of CD38-Targeted [Zr]Zr-DFO-Daratumumab for Imaging Multiple Myeloma.Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity in response remains a major challenge in MM. Cluster of differentiation 38 (CD38) is a type II transmembrane glycoprotein overexpressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is a U.S. Food and Drug Administration-approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [Zr]Zr-desferrioxamine (DFO)-daratumumab PET/CT imaging in MM tumor models. Daratumumab was conjugated to DFO--benzyl-isothiocyanate (DFO-Bz-NCS) for radiolabeling with Zr. Chelator conjugation was confirmed by electrospray ionization-mass spectrometry, and radiolabeling was monitored by instant thin-layer chromatography. Daratumumab was conjugated to Cyanine5 (Cy5) dye for cell microscopy. In vitro and in vivo evaluation of [Zr]Zr-DFO-daratumumab was performed using CD38 human myeloma MM1.S- (MM1.S) cells. Cellular studies determined the affinity, immunoreactivity, and specificity of [Zr]Zr-DFO-daratumumab. A 5TGM1- (5TGM1)/KaLwRij MM mouse model served as control for imaging background noise. [Zr]Zr-DFO-daratumumab PET/CT small-animal imaging was performed in severe combined immunodeficient mice bearing solid and disseminated MM tumors. Tissue biodistribution (7 d after tracer administration, 1.11 MBq/animal, = 4-6/group) was performed in wild-type and MM1.S tumor-bearing mice. A specific activity of 55.5 MBq/nmol (0.37 MBq/μg) was reproducibly obtained with [Zr]Zr-daratumumab-DFO. Flow cytometry confirmed CD38 expression (>99%) on the surface of MM1.S cells. Confocal microscopy with daratumumab-Cy5 demonstrated specific cell binding. Dissociation constant, 3.3 nM (±0.58), and receptor density, 10.1 fmol/mg (±0.64), was obtained with a saturation binding assay. [Zr]Zr-DFO-daratumumab/PET demonstrated specificity and sensitivity for detecting CD38 myeloma tumors of variable sizes (8.5-128 mm) with standardized uptake values ranging from 2.1 to 9.3. Discrete medullar lesions, confirmed by bioluminescence images, were efficiently imaged with [Zr]Zr-DFO-daratumumab/PET. Biodistribution at 7 d after administration of [Zr]Zr-DFO-daratumumab showed prominent tumor uptake (27.7 ± 7.6 percentage injected dose per gram). In vivo blocking was achieved with a 200-fold excess of unlabeled daratumumab. [Zr]Zr-DFO- and Cy5-daratumumab demonstrated superb binding to CD38 human MM cells and significantly low binding to CD38 cells. Daratumumab bioconjugates are being evaluated for image-guided delivery of therapeutic radionuclides.
Anchal Ghai, Dolonchampa Maji, Nicholas Cho, Chantiya Chanswangphuwana, Michael Rettig, Duanwen Shen, John DiPersio, Walter Akers, Farrokh Dehdashti, Samuel Achilefu, Ravi Vij, Monica Shokeen
2286 related Products with: Preclinical Development of CD38-Targeted [Zr]Zr-DFO-Daratumumab for Imaging Multiple Myeloma.0.1 mg1 mg25 µg4X1.25ml; 200 reactions ( 1 kit(s)
#28042324 2017/01/01 To Up
Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging.Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.
Xiangyu Yang, Zhe Wang, Fuwu Zhang, Guizhi Zhu, Jibin Song, Gao-Jun Teng, Gang Niu, Xiaoyuan Chen
#27723970 2016/10/21 To Up
Glutathione-Sensitive Hyaluronic Acid-SS-Mertansine Prodrug with a High Drug Content: Facile Synthesis and Targeted Breast Tumor Therapy.Low tolerability and tumor selectivity restricts many potent anticancer drugs including mertansine from wide clinical use. Here, glutathione-activatable hyaluronic acid-SS-mertansine prodrug (HA-SS-DM1) was designed and developed to achieve enhanced tolerability and targeted therapy of CD44+ human breast tumor xenografts. DM1 was readily conjugated to HA using 2-(2-pyridyldithio)-ethylamine as a linker. Notably, HA-SS-DM1 with a high DM1 content of 20 wt % had a mean size of ∼170 nm at concentrations above 0.2 mg/mL while transformed into unimers upon dilution to 0.04 mg/mL. HA-SS-DM1 exhibited a superior targetability to MCF-7 cancer cells with an exceptionally low IC of 0.13 μg DM1/mL. The pharmacokinetic studies displayed that Cy5-labeled HA-SS-DM1 had an elimination half-life of 2.12 h. Notably, HA-SS-DM1 displayed better tolerability with a maximum-tolerated dose 4-fold higher than free DM1. Cy5-labeled HA-SS-DM1 quickly accumulated in the MCF-7 tumor, the fluorescence intensity of which was maximized at 24 h post injection and kept strong in 48 h. The tumor Cy5 level reached 8.17%ID/g at 24 h. The therapeutic results demonstrated that HA-SS-DM1 effectively inhibited tumor growth at 800 μg DM1 equiv/kg while causing reduced side effects as compared to free DM1. Glutathione-cleavable HA-SS-DM1 prodrug with superior drug content, excellent targetability, enhanced tolerability, and easy large-scale synthesis appears to be a highly promising alternative to clinically used Trastuzumab emtansine (T-DM1) for targeted breast tumor therapy.
Ping Zhong, Jian Zhang, Chao Deng, Ru Cheng, Fenghua Meng, Zhiyuan Zhong
2136 related Products with: Glutathione-Sensitive Hyaluronic Acid-SS-Mertansine Prodrug with a High Drug Content: Facile Synthesis and Targeted Breast Tumor Therapy.96 tests96 tests
#27652266 2016/08/29 To Up
Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts.Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research.
Jianbo Li, Baoliang Bao, Lei Liu, Xuemei Wang
2474 related Products with: Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts.1 kit1 kit1 kit
#27444284 2016/07/21 To Up
In vivo imaging of tumour xenografts with an antibody targeting the potassium channel K10.1.The K10.1 (Eag1) voltage-gated potassium channel represents a promising molecular target for novel cancer therapies or diagnostic purposes. Physiologically, it is only expressed in the brain, but it was found overexpressed in more than 70 % of tumours of diverse origin. Furthermore, as a plasma membrane protein, it is easily accessible to extracellular interventions. In this study we analysed the feasibility of the anti-K10.1 monoclonal antibody mAb62 to target tumour cells in vitro and in vivo and to deliver therapeutics to the tumour. Using time-domain near infrared fluorescence (NIRF) imaging in a subcutaneous MDA-MB-435S tumour model in nude mice, we showed that mAb62-Cy5.5 specifically accumulates at the tumour for at least 1 week in vivo with a maximum intensity at 48 h. Blocking experiments with an excess of unlabelled mAb62 and application of the free Cy5.5 fluorophore demonstrate specific binding to the tumour. Ex vivo NIRF imaging of whole tumours as well as NIRF imaging and microscopy of tumour slices confirmed the accumulation of the mAb62-Cy5.5 in tumours but not in brain tissue. Moreover, mAb62 was conjugated to the prodrug-activating enzyme β-D-galactosidase (β-gal; mAb62-β-gal). The β-gal activity of the mAb62-β-gal conjugate was analysed in vitro on K10.1-expressing MDA-MB-435S cells in comparison to control AsPC-1 cells. We show that the mAb62-β-gal conjugate possesses high β-gal activity when bound to K10.1-expressing MDA-MB-435S cells. Moreover, using the β-gal activatable NIRF probe DDAOG, we detected mAb62-β-gal activity in vivo over the tumour area. In summary, we could show that the anti-K10.1 antibody is a promising tool for the development of novel concepts of targeted cancer therapy.
Joanna Napp, Luis A Pardo, Franziska Hartung, Lutz F Tietze, Walter Stühmer, Frauke Alves
2705 related Products with: In vivo imaging of tumour xenografts with an antibody targeting the potassium channel K10.1.100ug Lyophilized100ug Lyophilized100ug Lyophilized50μl100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized
#26840082 // To Up
Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2-overexpressing cancer cells.The therapeutic potential of RNA interference (RNAi) has been limited by inefficient delivery of short interfering RNA (siRNA). Tumor-specific recognition can be effectively achieved by antibodies directed against highly expressed cancer cell surface receptors. We investigated the utility of linking an internalizing streptavidin-conjugated HER2 antibody to an endosome-disruptive biotinylated polymeric nanocarrier to improve the functional cytoplasmic delivery of siRNA in breast and ovarian cancer cells in vitro and in an intraperitoneal ovarian cancer xenograft model in vivo, yielding an 80% reduction of target mRNA and protein levels with sustained repression for at least 96 hours. RNAi-mediated site specific cleavage of target mRNA was demonstrated using the 5' RLM-RACE (RNA ligase mediated-rapid amplification of cDNA ends) assay. Mice bearing intraperitoneal human ovarian tumor xenografts demonstrated increased tumor accumulation of Cy5.5 fluorescently labeled siRNA and 70% target gene suppression after treatment with HER2 antibody-directed siRNA nanocarriers. Detection of the expected mRNA cleavage product by 5' RLM-RACE assay confirmed that suppression occurs via the expected RNAi pathway. Delivery of siRNA via antibody-directed endosomolytic nanoparticles may be a promising strategy for cancer therapy.
Maria C Palanca-Wessels, Garrett C Booth, Anthony J Convertine, Brittany B Lundy, Geoffrey Y Berguig, Michael F Press, Patrick S Stayton, Oliver W Press
1946 related Products with: Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2-overexpressing cancer cells.1 module1mg1 module1 module1 module200 ug1 module1 module1 module1 module
#26490315 2015/10/21 To Up
Fluorescent Image-Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real Time.The inability to visualize cancer during prostatectomy contributes to positive margins, cancer recurrence, and surgical side effects. A molecularly targeted fluorescent probe offers the potential for real-time intraoperative imaging. The goal of this study was to develop a probe for image-guided prostate cancer surgery.
Geoffrey A Sonn, Andrew S Behesnilian, Ziyue Karen Jiang, Kirstin A Zettlitz, Eric J Lepin, Laurent A Bentolila, Scott M Knowles, Daniel Lawrence, Anna M Wu, Robert E Reiter
2151 related Products with: Fluorescent Image-Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real Time.100 0.1ml (1mg/ml)0.1ml (1mg/ml)0.1ml
#26288060 2015/08/28 To Up
PET Imaging of Dll4 Expression in Glioblastoma and Colorectal Cancer Xenografts Using (64)Cu-Labeled Monoclonal Antibody 61B.Delta-like ligand 4 (Dll4) expressed in tumor cells plays a key role to promote tumor growth of numerous cancer types. Based on a novel antihuman Dll4 monoclonal antibody (61B), we developed a (64)Cu-labeled probe for positron emission tomography (PET) imaging of tumor Dll4 expression. In this study, 61B was conjugated with the (64)Cu-chelator DOTA through lysine on the antibody. Human IgG (hIgG)-DOTA, which did not bind to Dll4, was also prepared as a control. The Dll4 binding activity of the probes was evaluated through the bead-based binding assay with Dll4-alkaline phosphatase. The resulting PET probes were evaluated in U87MG glioblastoma and HT29 colorectal cancer xenografts in athymic nude mice. Our results demonstrated that the 61B-DOTA retained (77.2 ± 3.7) % Dll4 binding activity of the unmodified 61B, which is significantly higher than that of hIgG-DOTA (0.06 ± 0.03) %. Confocal microscopy analysis confirmed that 61B-Cy5.5, but not IgG-Cy5.5, predominantly located within the U87MG and HT29 cells cytoplasm. U87MG cells showed higher 61B-Cy5.5 binding as compared to HT29 cells. In U87MG xenografts, 61B-DOTA-(64)Cu demonstrated remarkable tumor accumulation (10.5 ± 1.7 and 10.2 ± 1.2%ID/g at 24 and 48 h postinjection, respectively). In HT29 xenografts, tumor accumulation of 61B-DOTA-(64)Cu was significantly lower than that of U87MG (7.3 ± 1.3 and 6.6 ± 1.3%ID/g at 24 and 48 h postinjection, respectively). The tumor accumulation of 61B-DOTA-(64)Cu was significantly higher than that of hIgG-DOTA-(64)Cu in both xenografts models. Immunofluorescence staining of the tumor tissues further confirmed that tumor accumulation of 61B-Cy5.5 was correlated well with in vivo PET imaging data using 61B-DOTA-(64)Cu. In conclusion, 61B-DOTA-(64)Cu PET probe was successfully synthesized and demonstrated prominent tumor uptake by targeting Dll4. 61B-DOTA-(64)Cu has great potential to be used for noninvasive Dll4 imaging, which could be valuable for tumor detection, Dll4 expression level evaluation, and Dll4-based treatment monitoring.
Bin Zhou, Hui Wang, Ren Liu, Mengzhe Wang, Huaifu Deng, Benjamin C Giglio, Parkash S Gill, Hong Shan, Zibo Li
2502 related Products with: PET Imaging of Dll4 Expression in Glioblastoma and Colorectal Cancer Xenografts Using (64)Cu-Labeled Monoclonal Antibody 61B.100ug100ug100ug100ug100ug100100ug Lyophilized
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