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Preparation of 64Cu and its prospective carriers for nuclear medicine.
Kozempel, Ján ; Lešetický, Ladislav (advisor) ; Kotek, Jan (referee) ; John, Jan (referee) ; Příhoda, Jiří (referee)
5 Summary The preparation of 64Cu including it's radiochemical separation and the preparation of its novel radiolabelled tracers intended for the use in nuclear medicine is described in this work. A novel method for the preparation of no carrier added 64Cu, based on the 64Zn(d,2p)64Cu reaction and consecutive dual ion exchange chromatography was developed. The radiochemical product was of high specific activity and with only 61Cu radionuiclidic impurity, which allows it's use for in vitro laboratory experiments or in vivo preclinical tests of labelled tracers. We have focused on the preparation of several 64Cu labelled tracers. Two different types - water soluble polymer carriers and hypoxia selective biacetyl bis- (N4-alkylthiosemicarbazone) complexes of 64Cu were prepared. The water soluble polymer carriers based on the copolymers of NIPAM, GM and HPMA bearing various chelating groups were prepared. The polymeric chain was modified by copolymerization of a monomer with chelating functional group or modified after polymerization. Two standard polyacidic chelators (DOTA, DTPA) as well as three non-common copper chelators (dipicolylamine, thiosemicarbazide, Ag ionophore II) were used. Their potential use in nuclear medicine for local radio- or combined ...
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Bifunctional ligands for copper(II) complexation
Benešová, Martina ; Kotek, Jan (advisor) ; Kozempel, Ján (referee)
Title: Bifunctional ligands for copper(II) complexation Author: Bc. Martina Benešová Supervisor: doc. RNDr. Jan Kotek, Ph.D. Institution: Department of Inorganic Chemistry, Faculty of Science, CU in Prague Author's e-mail: EvaGlaser@seznam.cz ABSTRACT The main aim of this thesis was preparation of macrocyclic ligands based on 1,4,8,11- tetraazacyclotetradecane skeleton, which is suitable for selective complexation of divalent copper, and study of their properties. These ligands are suggested for potential utilization in nuclear medicine. Cyclam macrocycle was modified to bear one coordinating aminobenzylphospinate pendant arm (compound L1) or monophosphinate-bis(phosphonate) pendant arm (compound L2). During the synthesis, the skeleton was protected in positions 1, 4 and 8. In the frame of this work the synthesis of both targeted products was developed. Furthermore, a study of the thermodynamic, kinetic and coordination properties of ligand L2 was investigated by UV/VIS spectrophotometry and potentiometric titrations. A model bioconjugation of ligand L1 with primary amine was also studied. KEYWORDS Cyclam, phosphinates, phosphonates, nuclear medicine, copper(II) complexes, kinetic inertness, thermodynamic stability.
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The study of properties of radiolabelled monoclonal antibodies for imaging in oncology
Janoušek, Jiří ; Trejtnar, František (advisor) ; Kozempel, Ján (referee) ; Lázníčková, Alice (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Jiří Janoušek, MSc. Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Consultant: Mgr. Pavel Bárta, Ph.D. Title of doctoral thesis: The study of properties of radiolabelled monoclonal antibodies for imaging in oncology Monoclonal antibodies belong to the group of targeted biological drugs that are currently successfully applied in various medical specialties, including oncology. The ability to specifically bind to antigens present in a tumour tissue is their significant attribute that can be used for imaging tumours in Nuclear Medicine. Receptors for vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) are possible tumour specific targets that are characteristic for some types of proliferating tumour tissue. The attachment of appropriate radionuclide is necessary for the potential radiodiagnostic use of monoclonal antibody. This task requires chemical modification of the antibody molecule that can damage its immunoreactivity and the binding to the target receptor. The aim of the doctoral thesis was to study the influence of labelling conditions with selected diagnostic radionuclides on radiochemical characteristics, in vitro receptor specific binding and...
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The study of properties of radiolabelled monoclonal antibodies for imaging in oncology
Janoušek, Jiří ; Trejtnar, František (advisor) ; Kozempel, Ján (referee) ; Lázníčková, Alice (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Jiří Janoušek, MSc. Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Consultant: Mgr. Pavel Bárta, Ph.D. Title of doctoral thesis: The study of properties of radiolabelled monoclonal antibodies for imaging in oncology Monoclonal antibodies belong to the group of targeted biological drugs that are currently successfully applied in various medical specialties, including oncology. The ability to specifically bind to antigens present in a tumour tissue is their significant attribute that can be used for imaging tumours in Nuclear Medicine. Receptors for vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) are possible tumour specific targets that are characteristic for some types of proliferating tumour tissue. The attachment of appropriate radionuclide is necessary for the potential radiodiagnostic use of monoclonal antibody. This task requires chemical modification of the antibody molecule that can damage its immunoreactivity and the binding to the target receptor. The aim of the doctoral thesis was to study the influence of labelling conditions with selected diagnostic radionuclides on radiochemical characteristics, in vitro receptor specific binding and...
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Phytoextraction of radionuclides as the model of radiopharmaceutical residues decontamination
Krmelová, Tereza ; Smrček, Stanislav (advisor) ; Kozempel, Ján (referee)
Title: Phytoextraction of radionuclides as the model of radiopharmaceutical residues decontamination Author: Tereza Krmelová Branch: Environmental chemistry Type of thesis: Bachelor's Advisor: Doc. Ing. Stanislav Smrček, CSc Abstract: The aim is to demonstrate the possibility of 223 Ra extraction by root system tested plant species Avena sativa and Zea mays as a model phytoremediation technology and to obtain data to assess the possible entry of residues in food chains. It is also studied the possible effect of additives - complex agents and growth stimulators on uptake and translocation of contaminant from roots to shoot. It was confirmed the addition of additives EDTA, Atonic® , Sunagreen® , Rexan® , Stimulator Z® , Racine® , Vermaktiv Stimul® a Vermaktiv RP affect to uptake and translocation of the 223 Ra in the plant. Addition of stimulators reduces 223 Ra uptake 75% of the starting activity value from 24 to 71% for corn, but simultaneously increases the translocation the contaminant to shoots. The uptake is reduced from original 84% to 20-59% for oats. The uptake isn't affected for the experiments with added Sunagreen® and addition of EDTA causes only minimal uptake of studied contaminant. From the results it is evident that uptake of 223 Ra is possible. Commonly used growth regulators increase...
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Bifunctional ligands for copper(II) complexation
Benešová, Martina ; Kotek, Jan (advisor) ; Kozempel, Ján (referee)
Title: Bifunctional ligands for copper(II) complexation Author: Bc. Martina Benešová Supervisor: doc. RNDr. Jan Kotek, Ph.D. Institution: Department of Inorganic Chemistry, Faculty of Science, CU in Prague Author's e-mail: EvaGlaser@seznam.cz ABSTRACT The main aim of this thesis was preparation of macrocyclic ligands based on 1,4,8,11- tetraazacyclotetradecane skeleton, which is suitable for selective complexation of divalent copper, and study of their properties. These ligands are suggested for potential utilization in nuclear medicine. Cyclam macrocycle was modified to bear one coordinating aminobenzylphospinate pendant arm (compound L1) or monophosphinate-bis(phosphonate) pendant arm (compound L2). During the synthesis, the skeleton was protected in positions 1, 4 and 8. In the frame of this work the synthesis of both targeted products was developed. Furthermore, a study of the thermodynamic, kinetic and coordination properties of ligand L2 was investigated by UV/VIS spectrophotometry and potentiometric titrations. A model bioconjugation of ligand L1 with primary amine was also studied. KEYWORDS Cyclam, phosphinates, phosphonates, nuclear medicine, copper(II) complexes, kinetic inertness, thermodynamic stability.
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Preparation of 64Cu and its prospective carriers for nuclear medicine.
Kozempel, Ján ; Lešetický, Ladislav (advisor) ; Kotek, Jan (referee) ; John, Jan (referee) ; Příhoda, Jiří (referee)
5 Summary The preparation of 64Cu including it's radiochemical separation and the preparation of its novel radiolabelled tracers intended for the use in nuclear medicine is described in this work. A novel method for the preparation of no carrier added 64Cu, based on the 64Zn(d,2p)64Cu reaction and consecutive dual ion exchange chromatography was developed. The radiochemical product was of high specific activity and with only 61Cu radionuiclidic impurity, which allows it's use for in vitro laboratory experiments or in vivo preclinical tests of labelled tracers. We have focused on the preparation of several 64Cu labelled tracers. Two different types - water soluble polymer carriers and hypoxia selective biacetyl bis- (N4-alkylthiosemicarbazone) complexes of 64Cu were prepared. The water soluble polymer carriers based on the copolymers of NIPAM, GM and HPMA bearing various chelating groups were prepared. The polymeric chain was modified by copolymerization of a monomer with chelating functional group or modified after polymerization. Two standard polyacidic chelators (DOTA, DTPA) as well as three non-common copper chelators (dipicolylamine, thiosemicarbazide, Ag ionophore II) were used. Their potential use in nuclear medicine for local radio- or combined ...
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