Chaudhary P.,University of North Texas |
Thamake S.I.,University of North Texas |
Thamake S.I.,Radiomedix, Inc. |
Shetty P.,University of North Texas |
Vishwanatha J.K.,University of North Texas
British Journal of Cancer | Year: 2014
Background:Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown.Methods:The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, Clonogenic, and wound-healing assays were performed in this study.Results:We demonstrate that AnxA2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalisation by blocking its homodimerisation. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration.Conclusions:These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signalling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers. © 2014 Cancer Research UK.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.94K | Year: 2014
DESCRIPTION (provided by applicant): The American Cancer Society reports that death rates for melanoma have been rising in the United States for the past 30 years. It is one of the more common cancers in population younger than 30, and the most common cancer in adults ages 25 to 29. One characteristic of metastatic melanoma cells that is recognized as a potential target for new therapies is their elevated glucose metabolism - and concomitant upregulation of glucose transporters (e.g., GLUT1) and hexokinaseenzyme activity. Radiolabeled glucose (i.e., [18F]-FDG) has been the mainstay for imaging of metastatic melanoma for many years. There are no agents available that detect differences in melanoma metabolism and can be used for both imaging and targeted radiotherapy. This proposal is focused on development, validation and commercialization of novel class of theranostic [203/212]Pb-labeled glucosamine conjugates (RMX-GC) for targeted imaging and image-guided therapy of metastatic melanoma. Our innovative
Radiomedix, Inc. | Date: 2016-06-28
The present invention relates to the field of radiochemistry, nuclear imaging, radionuclide therapy and chemical synthesis. More particularly, it concerns a strategy for radiolabeling target ligands. It further concerns methods of using those radiolabeled ligands for imaging, radionuclide therapy and tissue-specific disease imaging.
Radiomedix, Inc. | Date: 2012-06-20
The invention provides D02S derivatives conjugated to monosaccharide ligands directly or through a linker and optionally chelated to a metal, wherein the D02S derivatives having the following structure: wherein R_(1), R_(2) are each independently OH or O-alkyl; R_(1 )is a hydrogen, a linker, or a ligand; R_(3 )is a linker and/or a ligand; and n is an integer from 1 to 10; the linker is an amino acid, a peptide, an amino alcohol, a polyethylylene glycol, an alkyl, an alkenyl, an alkynyl, an azide, an aromatic compound, a carboxylic acid, or an ester, the alkyl, alkenyl, or alkynyl is optionally substituted with an alkyl, a halogen, a nitro group, a hydroxyl group, an amino group, or a carboxyl group; the ligand is a GLUT1 targeting moiety.
Radiomedix, Inc. | Date: 2016-09-26
Pharmaceutical product, namely, radiolabelled pharmaceutical preparations that target neuroendocrine tumor cell surface receptors for the detection and localization of neuroendocrine tumors in cancer patients and for targeted diagnostic management of the neuroendocrine tumors in cancer patients.
Delpassand E.S.,Excel Diagnostics and Nuclear Oncology Center |
Delpassand E.S.,Radiomedix, Inc. |
Samarghandi A.,Excel Diagnostics and Nuclear Oncology Center |
Zamanian S.,Radiomedix, Inc. |
And 11 more authors.
Pancreas | Year: 2014
OBJECTIVE: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium 177 ( 177Lu) DOTATATE in patients with progressive NETs. METHODS: Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonrandomized, phase 2 clinical trial. Repeated cycles of 200 mCi (7.4 GBq; ±10%) were administered up to the cumulative dose of 800 mCi (29.6 GBq; ±10%). RESULTS: Among 32 evaluable patients, partial response and minimal response to treatment were seen in 28% and 3%, respectively, and stable disease was seen in 41% of patients. A total of 28% had progressive disease. A response to treatment was significantly associated with lower burden of disease in the liver. No significant acute or delayed hematologic or kidney toxicity was observed. An impressive improvement of performance status and quality of life were seen after 177Lu- DOTATATE therapy. CONCLUSIONS: Treatment with multiple cycles of 177Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated. This treatment results in control of the disease in most patients, whereas systemic toxicities are limited and reversible. Quality of life is also improved. Copyright © 2014 Lippincott Williams & Wilkins.
Radiomedix, Inc. | Date: 2012-03-02
Medical laboratory machines, namely, radiopharmaceutical synthesizing machines comprised of a series of valves, tubing, and reaction vials used to make radioisotope drugs.
PubMed | Radiomedix, Inc., Martin Luther University of Halle Wittenberg, Erasmus University Rotterdam, Zentralklinik Bad Berka and 2 more.
Type: Journal Article | Journal: Nature protocols | Year: 2016
Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system,(68)Ga(3+) of the generator eluate is trapped on a cation exchanger cartridge (100 mg, 8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of (68)Ga radiopharmaceuticals (12-16 min).
Radiomedix, Inc. | Date: 2015-01-22
Radiomedix, Inc. | Date: 2011-03-31
Radiopharmaceutical synthesizing machines comprised of a series of syringes, valves, tubing, disposable cassettes and reaction vials used to make radioisotopes for positron emission tomography for use in the diagnosis and treatment of cancer.