|
|
In vitro saturation study of radiolabelled monoclonal antibody carotuximab
Sladká, Anežka ; Bárta, Pavel (advisor) ; Nový, Zbyněk (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Anežka Sladká Supervisor: Mgr. Pavel Bárta, Ph.D. Thesis title: In vitro saturation study of radiolabeled monoclonal antibody carotuximab Angiogenesis, or the formation of new blood vessels from existing ones, is currently one of the processes targeted by cancer therapy, as the formation of new blood vessels is a prerequisite for successful tumor growth and eventual expansion in the body in the form of metastasis. One of the receptors involved in signalling leading to angiogenesis is endoglin (CD105). This receptor is also targeted by the chimeric monoclonal antibody carotuximab. The aim of this thesis was to perform indirect labelling of the monoclonal antibody carotuximab with the radionuclide gallium-67 using the bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). During the labelling process, the NODAGA:carotuximab molar ratio was optimized (1:20, 1:50 and 1:100). The prepared radiopharmaceutical [67 Ga]Ga-NODAGA-carotuximab was subsequently determined for its radiochemical purity by HPLC with radiometric detection. This was followed by in vitro binding experiments on human renal tumor cell culture involving internalization,...
|
|
|
In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line
Holodňáková, Nikola ; Bárta, Pavel (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Nikola Holodňáková Supervisor: Mgr. Pavel Bárta, Ph.D. Name of the work: In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line. Targeted biological treatment becomes more and more important with the development of a new therapy in oncology. It stimulates immune system to eliminate cancer cells. Significant progress has been made since the introduction of monoclonal antibodies. They represent one of the newest possibility used in diagnosis and treatment of tumours. The ability of the monoclonal antibody ramucirumab is to recognize and bind specifically to tumour cell antigens such as the VEGF type 2 receptor (VEGFR-2) and thus to supress angiogenic process. Anti-angiogenic ramucirumab inhibits this receptor via blocking of VEGF binding sites, which prevents the growth of tumours. It is possible to increase antitumor effect of monoclonal antibodies by their combination with other molecules like radionuclides, toxins and cytostatics when forming the so called conjugates. Prepared immunoconjugates serve as diagnostic and therapeutic tools also in Nuclear Medicine. The aim of the experimental work in was the preparation of...
|
|
|
Radiolabelling of Lys3-Bombesine and determination of stability of the radiolabelled product
Kosová, Pavla ; Lázníčková, Alice (advisor) ; Kubíček, Vladimír (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Biophysics and Physical Chemistry Consultant: Doc. Ing. Alice Lázníčková, CSc. Student: Pavla Kosová Title of thesis: Radiolabeling of PCTA-Lys3-Bombesine and determination of stability of the radiolabeled product The dissertation deal with study of radiolabeling of new receptor-specific peptide - bombesin, which was modified with chelator PCTA, PCTA-Lys3-bombesin, with radionuclide 177 Lu, and determination of labelled product quality and its stability. For quality control we used method high-efficiency liquid chromatography (HPLC) and thin-layer chromatography (ITLC) on ITLC-SG. HPLC offer clear proof about pollution and possible dissociative outputs. Comparison of both methods for determination of purity of labelled peptide showed that HPLC is more accurate than TLC method.
|
|
|
Transport and Metabolism of Radio-Labelled Cytokinins in Plant Cells and Tissues
Nedvěd, Daniel ; Ryšlavá, Helena (advisor) ; Vaňková, Radomíra (referee)
Cytokinins are a large group of phytohormones. Since their discovery in the 1950s, they have shown to play a pivotal role in plant physiology. Most studies so far focused on cytokinin action mechanisms and their metabolic regulation. Identification of AtABCG14 and AtPUP14 as cytokinin-specific membrane carriers brought researchers' attention to cytokinin membrane transport, too. In this thesis, we performed experiments with radio-labelled cytokinin tracers. We show that trans-zeatin and isopentenyladenine, two major biologically active cytokinins, are readily transported across the plasma membrane in tobacco BY-2 cell suspension. Making use of mathematical modelling, we show that BY-2 cells possess a membrane transport system with an affinity toward cytokinins. Next, we show that atabcg14 and atpup14 mutations affect cytokinin metabolism in Arabidopsis thaliana plants. Keywords: cytokinin, Arabidopsis thaliana, tobacco BY-2 cell lines, membrane transport, purine permease, ATP-binding cassette, radio-labelling
|
|
|
Radiolabeling of ramucirumab followed with the study of its internalization in vitro
Gajdoš, Jakub ; Bárta, Pavel (advisor) ; Kuchařová, Monika (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Bc. Jakub Gajdoš Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabeling of ramucirumab followed with the study of its internalization in vitro. The process of angiogenesis ensures the formation of the bloodstream at the site of its increased need. Therefore, it is not surprising that angiogenesis is often included in the tumor production process, because it provides the tumor cells nutrition supply and metabolite removal. The targeting of angiogenesis has become a key topic of some scientific research. The process of tumor blood supply formation provides a family of vascular endothelial factors (VEGFs) and their respective receptors, which have become the target of the angiogenesis attenuation in a cancer treatment. One of many therapeutics is the monoclonal antibody ramucirumab targeted against VEGF receptor type 2 (VEGFR-2). Radioactive labeling of ramucirumab with a suitable radionuclide could bring benefits in either radiotherapy or radiodiagnostics. The aim of this diploma thesis was the indirect radioactive labeling of monoclonal antibody ramucirumab using 99m Tc as radiodiagnostic nuclide via the chelation agent succinimidyl-6-...
|
|
|
In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line
Holodňáková, Nikola ; Bárta, Pavel (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Nikola Holodňáková Supervisor: Mgr. Pavel Bárta, Ph.D. Name of the work: In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line. Targeted biological treatment becomes more and more important with the development of a new therapy in oncology. It stimulates immune system to eliminate cancer cells. Significant progress has been made since the introduction of monoclonal antibodies. They represent one of the newest possibility used in diagnosis and treatment of tumours. The ability of the monoclonal antibody ramucirumab is to recognize and bind specifically to tumour cell antigens such as the VEGF type 2 receptor (VEGFR-2) and thus to supress angiogenic process. Anti-angiogenic ramucirumab inhibits this receptor via blocking of VEGF binding sites, which prevents the growth of tumours. It is possible to increase antitumor effect of monoclonal antibodies by their combination with other molecules like radionuclides, toxins and cytostatics when forming the so called conjugates. Prepared immunoconjugates serve as diagnostic and therapeutic tools also in Nuclear Medicine. The aim of the experimental work in was the preparation of...
|
|
|
Transport and Metabolism of Radio-Labelled Cytokinins in Plant Cells and Tissues
Nedvěd, Daniel ; Ryšlavá, Helena (advisor) ; Vaňková, Radomíra (referee)
Cytokinins are a large group of phytohormones. Since their discovery in the 1950s, they have shown to play a pivotal role in plant physiology. Most studies so far focused on cytokinin action mechanisms and their metabolic regulation. Identification of AtABCG14 and AtPUP14 as cytokinin-specific membrane carriers brought researchers' attention to cytokinin membrane transport, too. In this thesis, we performed experiments with radio-labelled cytokinin tracers. We show that trans-zeatin and isopentenyladenine, two major biologically active cytokinins, are readily transported across the plasma membrane in tobacco BY-2 cell suspension. Making use of mathematical modelling, we show that BY-2 cells possess a membrane transport system with an affinity toward cytokinins. Next, we show that atabcg14 and atpup14 mutations affect cytokinin metabolism in Arabidopsis thaliana plants. Keywords: cytokinin, Arabidopsis thaliana, tobacco BY-2 cell lines, membrane transport, purine permease, ATP-binding cassette, radio-labelling
|
|
|
The preparation and the following in vitro saturation study of the radiopharmaceutical 99mTc-DTPA-ramucirumab on PC-3 cell line
Sabolová, Klaudia ; Bárta, Pavel (advisor) ; Janoušek, Jiří (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Klaudia Sabolová Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: The preparation and the following in vitro saturation study of the radiopharmaceutical 99m Tc-DTPA-ramucirumab on PC-3 cell line In cancer treatment, immunology is given prominence, which compared with chemotherapy and radiotherapy has a lower risk of side effects on healthy tissues. Immunotherapy includes application of monoclonal antibodies aimed at some tumour antigens using either non conjugated monoclonal antibodies or conjugated ones with an appropriate effector element, such as radionuclide. Angiogenesis plays the important role in pathogenesis of tumour diseases. Angiogenic process is regulated mostly by the interactions among vascular growth factors (VEGFs) and VEGF receptors (VEGFR). The main regulator of angiogenesis is VEGF-A. The blocking of the interaction among VEGF-A and its receptors VEGFR-1 and VEGFR-2 inhibits angiogenesis, and so does the growth of tumours. Ramucirumab is the monoclonal antibody with antiangiogenic effect, which blocks this interaction by its binding to the extracellular VEGFR-2 domain with high affinity. The presented study is focused on ramucirumab...
|
|
|
Radiolabeling of ramucirumab followed with the study of its internalization in vitro
Gajdoš, Jakub ; Bárta, Pavel (advisor) ; Kuchařová, Monika (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Bc. Jakub Gajdoš Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabeling of ramucirumab followed with the study of its internalization in vitro. The process of angiogenesis ensures the formation of the bloodstream at the site of its increased need. Therefore, it is not surprising that angiogenesis is often included in the tumor production process, because it provides the tumor cells nutrition supply and metabolite removal. The targeting of angiogenesis has become a key topic of some scientific research. The process of tumor blood supply formation provides a family of vascular endothelial factors (VEGFs) and their respective receptors, which have become the target of the angiogenesis attenuation in a cancer treatment. One of many therapeutics is the monoclonal antibody ramucirumab targeted against VEGF receptor type 2 (VEGFR-2). Radioactive labeling of ramucirumab with a suitable radionuclide could bring benefits in either radiotherapy or radiodiagnostics. The aim of this diploma thesis was the indirect radioactive labeling of monoclonal antibody ramucirumab using 99m Tc as radiodiagnostic nuclide via the chelation agent succinimidyl-6-...
|
|
|
Radiolabelled receprot-specific peptides for cancer diagnosis and therapy
Parýzková, Barbora ; Bárta, Pavel (advisor) ; Trejtnar, František (referee)
Charles University Fakulty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Bc. Barbora Parýzková Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabelled receptor-specific peptides for cancer diagnosis and therapy. The presented diploma thesis is based on literature review and it deals with receptor- specific radioactive labeled peptides and their usage in the cancer diagnostic and treatment. It focuses on general knowledge about radiopharmaceuticals, further on the descriptions of either diagnostic or therapeutic radionuclides as well as on currently used chelating agents. The particular attention is paid to peptides like somatostatin and cholecystokinin and their usability in Nuclear Medicine for the imaging and treatment of certain malignancies. The other stated peptides in this diploma thesis are bombesin, vasoactive intestinal peptide and alpha melanocyte stimulating hormone. Keywords: receptor-specific peptides, radiolabelling, radionuclides for diagnosis and therapy, radiotherapy, radiodiagnostics, octreotide.
|
guest ::
