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Analysis of the Biological Behavior of Receptor-Specific Radiopharmaceuticals in Vitro
Melicharová, Ludmila ; Lázníček, Milan (advisor) ; Pávek, Petr (referee) ; Komárek, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of: Pharmacology and Toxicology Candidate: PharmDr. Ludmila Melicharová Supervisor: Prof. PharmDr. Ing. Milan Lázníček, PhD. Title of Doctoral Thesis: Analysis of the biological behavior of receptor-specific radiopharmaceuticals in vitro In the present work were studied receptor-specific radiopharmaceuticals and their biological behavior. Studies were performed with radiolabelled somatostatin and gastrin analogues. All of these substances are potentially useful in the diagnosis and therapy of neuroendocrine tumors. Somatostatin analogues under study: DOTA-TATE and DOTA-NOC labelled with 111 indium, 177 lutetium, 90 yttrium and 125 iodine. The studies were performed on AR42J cell line (rat pancreatic tumour cells). Internalization rate of these analogues and their specific binding to the cells with high density of appropriate receptors were determined. The data were compared with values obtained after intravenous administration of the same peptides to rats. The uptake of radioactive peptides in tissues with high density of somatostatin receptors in vivo were correlated with the results obtained in vitro conditions. We have compared four 111 In labelled gastrin analogues (so called minigastrins /MG/, namely MG11, MG45,...
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Study of Radiolabeling of PAMAM Dendrimers of 1st and 4th Generation with Diagnostic and Therapeutic Radionuclides
Biricová, Veronika ; Lázníčková, Alice (advisor) ; Kafka, Petr (referee) ; Komárek, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate Mgr. Veronika Biricová Supervisor Doc. Ing. Alice Lázníčková, CSs. Title of Doctoral Thesis Study of radiolabeling of PAMAM dendrimers of 1st and 4th generation with diagnostic and therapeutic radionuclides. Treatment and diagnosis of diseases using radioactive isotopes is important field on which pharmaceutical research is focused. In order to obtain drug which would specifically bind to receptors released by cells of affected organs and tissues and concurrently provide them a high dosage of radiation, one part of research projects is focused on finding carriers and also new metal chelators suitable for binding in a high number on biologically active molecule. This dissertation thesis is focused on a research of a new bifunctional chelator of trivalent metal ions bound in a high number on a branched dendrimer. Different parameters evaluating suitability of chelator for bond creation with radioactive istotopes were reviewed. From the biggest part is this thesis focused on labeling of dendrimer macromolecules with ligands bound on their surface with three different radioactive isotopes. Success of the labeling under different conditions based on value of radiochemical purity...
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Macrocyclic chelators for metal-radionuclides
Málková, Michaela ; Hermann, Petr (advisor) ; Příhoda, Jiří (referee) ; Komárek, Pavel (referee)
5 Abstract in English Complexation properties of structurally related macrocyclic polyazachelators with different metal ions suitable for a medicinal use were studied. In the present work, a study of chelators formally derived from H4dota (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) by replacement of one or four carboxylic groups with a phosphorus acid moiety(ies) was performed. Three new chelators were studied: H4do3apABn (10-{[(4-aminobenzyl)hydroxyphosphoryl]methyl}- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid), H5do3apPrA (10-{[(2-carboxyethyl)hydroxyphosphoryl]methyl}- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid), H4dotpOEt [1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrakis(methylphosphonic acid monoethylester)] In addition new data on stability constants of transition metal complexes of H5do3ap, 10-[(dihydroxyphosphoryl)methyl]- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, are presented. The achieved results suggest that all studied chelators form complexes with di- and trivalent metal ions with sufficient thermodynamic stability and kinetic inertness for the potential medicinal applications. The formation rate of complexes of the monophosphonic/inic chelators is comparable to that of the H4dota complexes. The formation rate of the complexes depends highly on...
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Study of Transport Mechanisms of Receptor-Specific Radiopharmaceuticals in the Kidney Cells.
Cihlo, Jan ; Lázníček, Milan (advisor) ; Šimůnek, Tomáš (referee) ; Komárek, Pavel (referee)
Renal accumulation of radiolabelled receptor specific substances can represent clinical problems for diagnosis and therapy of some typical malignancies due to radionephrotoxicity of these substances. The aim of this work was to design a suitable in vitro model for evaluating cumulative disposals of studied radiopharmaceuticals in the kidney and for finding possible mechanisms reducing the reabsorption of these substances by renal tubular cells. The suggested model designed for this purpose provides another opportunity for evaluation of their radionephrotoxical potential. The aforementioned in vitro method was standardised and used for the study of transport mechanism of some representatives of radiolabelled somatostatin analogues (111In/125I/90Y/177Lu-DOTA-Tyr3-octreotate, 111In/90Y/177Lu-DOTA-1-Nal3-octreotide), antibodies (111In/90Y/99mTc-AntiCD66) and albumin (FITC-albumin, 99mTc-albumin). All studied radioactive substances were radiolabelled with good practice and analyzed using HPLC and/or ITLC-SG methods. The radiolabelling technique of all studied specifically acting substances (radiolabelled peptides and antibodies) and also any concrete radionuclide showed no significant influence over the internalization into the renal OK cells. The difference of the internalized amount of FITC-albumin and...
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Hodnocení sortimentu podzimních aster z rodů Symphyotrichum a Eurybia
Komárek, Pavel
This bachelor's thesis mainly deals with the preliminary assessment of the range of genera of North American asters from Eurybia Cassini and Symphyotrichum Ness genus. Furthermore, their history, morphological, physiological, cultivation and the breeding aspect. It was provisionally evaluated 24 kinds and varieties of Symphyotrichum Ness genus and existing range of collections ZF MENDELU expanded to 140 pieces of North American asters.
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