v anglickom jazyku Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: František Lach Supervisor: Mgr. Pavel Bárta, PhD Consultant: Mgr. Lucie Hyršová Title of diploma thesis: In vitro saturation study of 99m Tc-HYNIC-ramucirumab on PC-3 cell line The number of malignant tumours in the population has increased in recent years. Due to the frequent serious sides effects of chemotherapeutic drugs on the whole organism, targeted antitumor therapy is at the forefront. Due to its specific effect on the regulatory and signal pathways of protein structures, monoclonal antibodies are used for the target anti-tumour therapy. The basic properties of the growing tumour include vasculogenesis (the ability to build new blood vessels from the endothelial precursors) and angiogenesis (the process of self-inducing formation of blood vessels). Endothelial tumour progenitors include vascular endothelial growth factor (VEGF). VEGF activates its biological activity by binding to its transmembrane tyrosine-kinase receptors VEGFR. Indeed, the inhibition of the vascular endothelial factor receptors is the target of some monoclonal antibodies. Ramucirumab is a monoclonal antibody that selectively inhibits VEGF receptor type 2 (VEGFR-2) and thereby...

Traffic efficiency applications over road networks have been investigated recently using VANETs. This area of research is primarily concerned with increasing the traffic fluency over road networks. In this thesis, we first propose an efficient and accurate protocol to detect congested road segments in a downtown area using VANETs. We refer to this protocol as the Efficient COngestion DEtection (ECODE) protocol. ECODE evaluates three different traffic characteristics of each road segment including traffic speed, traffic density, and the time required to travel the segment. Moreover, ECODE evaluates traffic characteristics and detects the congestion level in each direction of the road segment. In addition, we propose an intelligent, dynamic, distributed, and real-time path recommendations protocol. We refer to this protocol as Intelligent path reCOmenDation (ICOD) protocol. ICOD is the first path recommendation protocol that does not rely on a central database of gathered traffic data for each area of interest. Eliminating centralized behavior resolves bottleneck as well as single point of failure problems, which in turn minimizes congestion and collision problems in VANETs. Furthermore, ICOD selects the path towards each destination in a hop-by-hop manner, which makes the turn decision at each road intersection more accurate and real-time. Different variants of ICOD are introduced that consider travel time, travel distance, fuel consumption, gas emissions, and context-awareness of each road segment parameters. Moreover, two traffic balancing mechanisms are proposed in this thesis to distribute traffic over the road network evenly, namely Bal-Traf and Abs-Bal. These mechanisms eliminate the highly congested road segment scenarios that are caused by the path recommendation protocol. Bal-Traf detects and eliminates the highly congested output road segment at each road intersection. However, Abs-Bal aims to keep the traffic density balanced among all output road segments at each road intersection. Finally, we propose an Intelligent Traffic Light Controlling (ITLC) algorithm to schedule the phases of each traffic light at isolated road intersections. This algorithm aims to decrease the queuing delay time of competing traffic flows and to increase the throughput of each signalized road intersection. ITLC has also been adapted in this thesis to the Arterial Traffic Lights (ATLs) algorithm for arterial road network scenarios. In ATLs the expected platoons on the arterial street are considered in the scheduling algorithm of each traffic light located on the arterial street coordinates. Transmitting packets among these traffic lights report the main characteristics of each predicted platoon.

v anglickom jazyku Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Juliána Klimová Supervisor: Mgr. Pavel Bárta, Ph.D. Name of the work: In vitro saturation study of 99m Tc-HYNIC-ramucirumab on SKOV3 cell line. The passive immunotherapy is based on the use of already active immune system components (monoclonal antibodies), which play an important role in cancer cells elimination in the organism. The active immunotherapy tries to stimulate an active anticancer response via an appropriate form of an immunization. When monoclonal antibodies bind to cancer cells, those cells become a selected target for the following removal. The enhancement of the anti- cancer affect of monoclonal antibodies is possible due to the attachment of therapeutic agents like cytostatics, toxins and radionuclides. This presented master thesis is focused on the radiolabeling of the monoclonal antibody ramucirumab, which is directed against the vascular endothelial growth factor type 2 (VEGFR 2), which is often present in cells of some types of cancerous diseases. Within the experimental work, at first, there was a conjugation of chelating agent succinimidyl-6-hydrazino-nicotinamide (HYNIC) on the monoclonal antibody. After this step, radionuclide 99m...

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-...