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AbstractAbstract
[en] The main objective of this thesis can be divided into three parts. The first part deal with the investigation of optimum conditions for labeling of Colchicine (Col.) via electrophilic substitution reaction. The second part involves the electrophilic radioiodination of nitrofurantoin (NF). The third part involves the nucleophilic radioiodination of 3-iodo-4,5-diphenyl-1H-pyrazolo [3,4-C] pyridazine (3-IPP).1-Electrophilic radioiodination of colchicine with iodine-125 is carried out. The reaction parameters studied were colchicine concentration, ph of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of colchicine and to obtain a high radiochemical yield of the I125-colchicine (I125-Col). Using 3.7 MBq of NaI125, 1.25 mM of colchicine as substrate, 1.1 mM of chloramine-T (CAT) as oxidizing agent in ethanol at 60 degree C for 5 min a maximum radiochemical yield of I125-Col (60%) was obtained. The specific activity of I125-Col obtained was 44.4 MBq/0.5mmol, and the labeled compound was not completely separated and purified from Col by means of high performance liquid chromatography (HPLC), so the uncertainty in the purity may affect the distribution and clearance routes due to the expected competition between I125-Col and Col. The biological distribution in normal mice indicates the suitability of radioiodinated colchicine for imaging of muscles.2-Electrophilic radioiodination of Nitrofurantoin (NF) was performed. In order to obtain the optimum conditions, we study the effect of some factors which are expected to be affected on the radiochemical yield, such as: the effect of substrate, chloramines-T concentration, reaction temperature (25-80 degree C) with time and ph of the solution (2-11). The maximum labeling yield (90%) was obtained by using 3.7 MBq of NaI125, 1 mM of CAT as oxidizing agent in the ph 2, 1 mM of NF as substrate in DMF, at 60 degree C for 5 min. The specific activity of I125-NF obtained was 33.3 MBq/0.2 mmol, and the labeled compound was completely separated and purified from NF by means of high performance liquid chromatography (HPLC), The biological distribution in normal mice indicates the suitability of radioiodinated nitrofurantoin for imaging of urinary tract infection. 3-Nucleophilic radioiodination of 3-iodo-4,5- diphenyl-1H-pyrazolo [3,4-C] pyridazine (3-IPP) with iodine-125 was performed via I125 for I isotopic exchange reaction. The exchange reaction was achieved in different organic media such as acetone, dimethyl formamide (DMF), ethanol and ethyl acetate. The reaction temperature has a great effect on the labeling yield in case of DMF or ethanol as a reaction medium. The activation energies were calculated to be 4.6 Kcal/mol (19.3kJ/mol) in case of DMF as a reaction medium without phase transfer catalyst and 3.3 Kcal/mol (13.8kJ/mol) in the presence of tetra-butyl ammonium bromide (TBAB) as a phase transfer catalyst. These values are low compared with the calculated activation energy in the case of ethanol 9.2 Kcal/mol (38.5kJ/mol). The maximum radiochemical yield of 3-I125PP (92%) was obtained by drying 20 μ L (74 MBq) NaI125 in the reaction flask via the vacuum line and then adding the mixture of 150 μ L of 3-I125PP (1mg/mL in DMF) and 50 μL TBAB (1mg/mL in DMF) at 160 degree C within 5 min. The specific activity of 3-I125PP obtained was 68MBq/0.377 mmol. The labeled product was purified by means of high pressure liquid chromatography (HPLC). The biological distribution in normal mice indicates the suitability of 3-I125PP for imaging of brain and muscles.
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Source
2010; 120 p; Available from Liaison Officer for Egypt. Free of charge; 3-8 tabs;3-20 figs;115 refs; Thesis(Ph.D.)
Record Type
Miscellaneous
Literature Type
Thesis/Dissertation
Country of publication
ALCOHOLS, ALKALI METAL COMPOUNDS, ALKALOIDS, AMINES, ANIMALS, ANTIMITOTIC DRUGS, ANTIPYRETICS, AZINES, AZOLES, BETA DECAY RADIOISOTOPES, BODY, CENTRAL NERVOUS SYSTEM, CENTRAL NERVOUS SYSTEM AGENTS, CENTRAL NERVOUS SYSTEM DEPRESSANTS, CHEMICAL REACTIONS, DAYS LIVING RADIOISOTOPES, DRUGS, ELECTRON CAPTURE RADIOISOTOPES, ENERGY, HALIDES, HALOGEN COMPOUNDS, HALOGENATION, HETEROCYCLIC COMPOUNDS, HYDROXY COMPOUNDS, INORGANIC PHOSPHORS, INTERMEDIATE MASS NUCLEI, INTERNAL CONVERSION RADIOISOTOPES, IODIDES, IODINE COMPOUNDS, IODINE ISOTOPES, ISOTOPES, MAMMALS, NERVOUS SYSTEM, NUCLEI, ODD-EVEN NUCLEI, ORGANIC CHLORINE COMPOUNDS, ORGANIC COMPOUNDS, ORGANIC HALOGEN COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, ORGANS, PHOSPHORS, RADIOISOTOPES, RODENTS, SODIUM COMPOUNDS, VERTEBRATES
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