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Study of plasma protein binding of radiopharmaceuticals
Hafinec, Václav Matyáš ; Lázníček, Milan (advisor) ; Ramos Mandíková, Jana (referee)
Study of Plasma Protein Binding of Radiopharmaceuticals Summary The purpose of this work is the study of binding of substances (177 Lu-DOTA- [Lys3]bombesin, 177 Lu-NOTA-[Lys3]bombesin, 177 Lu-PCTA-[Lys3]bombesin, and 177 Lu- DOTA-MG47) to plasma proteins by equilibrum dialysis in 37řC, particularly using plasma samples of beef, rabbit, rat and human. Within this group, these substances were compared interspecifically. The substances 177 Lu-DOTA-[Lys3]bombesin, 177 Lu-NOTA-[Lys3]bombesin, 177 Lu- PCTA-[Lys3]bombesin, and 177 Lu-DOTA-MG47 are the newly developed receptor- specific radiolabeled peptides. For all the newly collected data, the interspecific comparison and subsequent statistical evaluation was performed. The indicated bombesin derivates were compared and statistically analyzed even between themselves. During the interspecies comparisons and the determination of the statistical significance of the data, there were found statistically significant and statistically highly significant differences between some of the examined samples. A highly significant difference was found during comparing with samples of 177 Lu-NOTA- [Lys3]bombesin and statistical evaluation, there was found a statistically highly significant difference. Despite the differences found, it is clear that the plasma binding concerning...
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Study of plasma protein binding of new radiopharmaceuticals
Šejnová, Barbora ; Lázníček, Milan (advisor) ; Melicharová, Ludmila (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ Department of Pharmacology and Toxicology DIPLOMA THESIS: Study of plasma protein binding of new radiopharmaceuticals SUMMARY: The binding ability of two receptor specific peptides - 111 In - DOTA - minigastrin 45 and 177 Lu - DOTA - bombesin - was studied by methods of equilibrium dialysis at 37řC and ultrafiltration in terms of interspecies comparison. Among selected animal species (rat, rabbit, bovine, human) was plasma protein binding completely different. Higher binding was observed for 111 In - DOTA - minigastrin 45. In comparison of both methods - higher values of binding were measured for both peptides and all species by ultrafiltration than by equilibrium dialysis. KEYWORDS: radiopharmaceuticals, plasma protein binding, equilibrium dialysis, ultrafiltration, 111 In - DOTA - minigastrin 45, 177 Lu - DOTA - bombesin Barbora Šejnová Hradec Králové 2011
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Determination of radiochemical purity and stability of new radiopharmaceuticals
Vorlová, Nikola ; Lázníček, Milan (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Nikola Vorlová Supervisor: Prof. PharmDr. Ing. Milan Lázniček, CSc. Title of diploma thesis: The determination of radiochemical purity and stability of newly developed radiopharmaceuticals. The theme of this thesis is determination of radiochemical purity and stability of newly developed radiopharmaceuticals from the group of receptor specific peptides and antibodies by using liquid chromatography - HPLC and thin layer chromatography ITLC -SG method. The antibody sample 177Lu-hR3-I has been studied in the theses( 177 Lu enters in to relation with modified antibody Nimotuzumab), which blocs EGF receptors and due to this fact the growth of tumor cells too. It has been detected, that it is necessary for reaching sufficient radiochemical purity to clean this radio-labeled antibody by the gel chromatography after labeling. Radio-chemical purity of this sample circulate from 99,46 % to 88,77 % during period of 6 days. Another samples have been studied, 111In-minigastrin - radioisotope 111 In linked up to three different minigastrins I, II, and III. Minigasrins are gastrin derivates , which have a very good absorptive capacity to receptors for cholecystokinin (CCK-B receptors) occurring in...
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Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics
Čepa, Adam ; Lázníček, Milan (advisor) ; Komárek, Pavel (referee) ; Melichar, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmacology and Toxycology Candidate Adam Cepa, MSc. Supervisor Prof. PharmDr. Ing. Milan Laznicek, CSc. Title of Doctoral Thesis Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics Special oncology diagnostics require new types of selective radiopharmaceuticals, especially those that are suitable for molecular PET imaging and therapy, respectively, teranostics. The aim of this work is to present a new target radiopharmaceutical for immunoPET diagnosis and therapy based on the monoclonal antibody IgG M75 directed to human carbonic anhydrase IX, nimotuzumab (hR3) target epidermal growth factor receptor (EGFR) and one of the bombesin derivatives (BBN) repeats. These molecules were labeled with radionuclides 64Cu (t1/2 12.70 hours), 61Cu (t1/2 3.33 hours), 68Ga (t1/2 68 min), 177Lu (t1/2 6.71 days). These potential radiopharmaceuticals were evaluated in vitro and in vivo. The IgG M75 antibody and its scFv-Fc M75 fragment were prepared by the genetic modification were conjugated to a specific chelator specific phosphinate (PHS) and radiolabeled by the radionuclides 61,64Cu. The stability of the labeled conjugate was tested in human...
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Preparation of radiolabeled albumin
Suchan, Martin ; Trejtnar, František (advisor) ; Lázníček, Milan (referee)
Objectives: This senior thesis was aimed at determining a method of albumin labelling with a particular radionuclide - technetium 99m Tc. Our task was to review the various possible methods needed for working out a procedure for albumin labelling with the mentioned radioisotope and also to test the behavior of labelled albumin in vitro in experiments with newly-isolated rat kidney cells. The next objectives of this work were to analyze the performed experiments, compare the results with other known procedures of albumin labelling with technetium 99m Tc and cast the results in the form of a scientific statement. Methods: A low pH and high concentration of albumin were useful for the albumin labelling experiments. A solution of SnCl2.2H2O was used for the reduction of pertechnetate. Purification of labelled albumin was performed by gel chromatography with a Sephadex G-50. The locations of albumin peaks in the chromatographic fractions were determined by the bicinchonic method. The location of pertechnetate was found by investigating the chromatographic spectrum of pertechnetate. Investigation of the elution spectrum was used to check for proper labelling. The radiochemical purity of labelled albumin was verified by paper chromatography and subsequent detection. Newly- labelled albumin was used in the...
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Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics
Čepa, Adam ; Lázníček, Milan (advisor) ; Komárek, Pavel (referee) ; Melichar, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmacology and Toxycology Candidate Adam Cepa, MSc. Supervisor Prof. PharmDr. Ing. Milan Laznicek, CSc. Title of Doctoral Thesis Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics Special oncology diagnostics require new types of selective radiopharmaceuticals, especially those that are suitable for molecular PET imaging and therapy, respectively, teranostics. The aim of this work is to present a new target radiopharmaceutical for immunoPET diagnosis and therapy based on the monoclonal antibody IgG M75 directed to human carbonic anhydrase IX, nimotuzumab (hR3) target epidermal growth factor receptor (EGFR) and one of the bombesin derivatives (BBN) repeats. These molecules were labeled with radionuclides 64Cu (t1/2 12.70 hours), 61Cu (t1/2 3.33 hours), 68Ga (t1/2 68 min), 177Lu (t1/2 6.71 days). These potential radiopharmaceuticals were evaluated in vitro and in vivo. The IgG M75 antibody and its scFv-Fc M75 fragment were prepared by the genetic modification were conjugated to a specific chelator specific phosphinate (PHS) and radiolabeled by the radionuclides 61,64Cu. The stability of the labeled conjugate was tested in human...
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Interspecies comparison of plasma protein binding of two radiolabelled complexes
Smolová, Lenka ; Lázníček, Milan (advisor) ; Trejtnar, František (referee)
This paper engages in the newly prepared bifunctional chelate DTPA-oxn which has a potential use in radiolabelling biological macromolecules. The aim of the paper was to prepare a radiolabelled bifunctional chelate DTPA-oxn with a suitable radionuclide, the 90Y has been used. Binding of 90Y-DTPA-oxn to human, bovine, rabbit and rat plasma protein was determined. An equilibrium dialysis at 37řC was employed for the plasma protein binding determination. The received results received were compared with the results of plasma protein binding of a clinically routinely used bifunctional chelate DTPA radiolabelled with 99mTc (99mTc-DTPA). The results showed a low plasma protein binding of these radiolabelled chelates. Interspeices comparison demonstrated that the results obtained for human, bovine and rat plasma are comparable, whereas those obtained for rabbit plasma are higher. This brings a conclusion that the binding of 90Y-DTPA- oxn and 99mTc-DTPA to plasma protein is not a factor that can influence their biological behavior.
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Study of plasma binding of receptor-specific peptides
Gregor, David ; Lázníček, Milan (advisor) ; Trejtnar, František (referee)
The binding ability of two receptor specific peptides namely 90Y-DOTA-TATE and 111In-DOTA-TATE was studied in therm of interspecies comparison by the method of equilibrium dialysis. This plasma protein binding was different for the chosen animal species (human, rat, rabbit, bovine eventually pork) whereas binding of 90Y-DOTA- TATE was higher than binding of 111In-DOTA-TATE. KEYWORDS: Protein binding, radiofarmaceuticals, equilibrium dialysis, 90Y-DOTA-TATE, 111In- DOTA-TATE
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