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العنوان
Synthesis, Radiolabeling and Evaluation of some Specific Probes for Malignant Melanoma Imaging /
المؤلف
Aglan, Hany Abd El-Hamid Abd El-Aziz.
هيئة الاعداد
باحث / هانى عبد الحميد عبد العزيز عجلان
مشرف / أحمد فوزي الكفراوي
مشرف / أسامة صديق عبد الغفار
مشرف / شعبان عبد الله قنديل
تاريخ النشر
2017.
عدد الصفحات
181 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Organic Chemistry
تاريخ الإجازة
1/1/2017
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء
الفهرس
Only 14 pages are availabe for public view

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from 180

Abstract

This chapter deals with an overview of using nuclear medicine and radiopharmaceuticals for diagnosis and treatment of human tumors disease. from all radioisotopes, radioiodine and radiofluorine are the most frequently used in the nuclear medicine. The methods used for radiolabelling are the electrophilic technique using an oxidizing agent such as chloramines–T and iodogen, and nucleophilic technique. It includes an information about human skin and types of skin cancers especially melanoma which is the most malignant one because it spread to almost every organ. It contains also a review for different compounds used before for melanoma imaging in nuclear medicine.
Chapter II: Experimental and Methodology
This chapter contains detailed information of the chemicals, reagents, radionuclides and equipment used in the study. It includes the synthesis of the relevant compounds and its characterization by mass and nuclear magnetic resonance spectroscopy. It involves also the labeling of benzamide derivatives by 125I using electrophilic substitution and nicotinamide derivatives by 18F. The separation and the purification of the relevant compounds were done by:-
1- Thin layer chromatography
2- High-pressure liquid chromatography
Chapter III: Results and Discussion
This study is divided into two parts:
The first part composes of:
1. The synthesis of some benzamides derivatives,
2. Studying the parameters that affect their radiodination by 125I,
3. Determination of their radiochemical yields and purity,
4. Studing the biodistribution of these radiotracers in mice.
The second part composes of:
1. The synthesis of two nicotinamide derivatives,
2. Labeling of them with 18F,
3. Determination of their radiochemical yields and purity,
4. In-vitro and in-vivo studies for these radiotracers.
In more details:
The first part:
1- The synthesis of benzamide 1 was simply performed using PYCIU as coupling reagent with good yield, 70.5 %, and in a short time, < 1 h. The radioiodination of benzamide 1 by iodine-125 was carried out via an electrophilic substitution reaction. The factors affecting the percent of radiochemical yields such as substrate concentration, pH of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied. The labeled compound was isolated and purified by means of TLC and HPLC. The maximum radiochemical yield, 90 %, was obtained with radiochemical purity greater than 98%. The log P value for [125I]benzamide 2 was measured as 2.7 ± 0.8.
2- Benzamide 5 was simply synthesized in three steps. The radioiodination of Benzamide 5 by iodine-125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76 %, was obtained with radiochemical purity greater than 99%. The log P value for [125I] Benzamide 6 was measured as 4.5± 0.3.
3- The synthesis of benzamide 7 was simply achieved in three steps like benzamide 5. The radioiodination step was carried out with 125I via an electrophilic substitution reaction. The reaction conditions were optimized. The labeled compound was purified by HPLC. The maximum radiochemical yield was found to be 78% at a radiochemical purity of 98%. The log P value for [125I]benzamide 8 was found as 3.96 ± 0.5.
The second part:
In this part, the rapid synthesis of two nicotinamide derivatives namely, nicotinamide 2 and nicotinamide 3 has been simply performed. They have been labeled by 18F and the radiochemical yield for [18F]nicotinamide 2 was 52 % with radiochemical purity 99 % and for [18F]nicotinamide 3 was 65 % with radiochemical purity 99 %. The labeled compounds were isolated and purified by HPLC. To evaluate the uptake of the radiotracers in-vitro, three kinds of cells, namely, Melur (melanin free), KB-3 carcinoma cell line (non-melanoma) and B16-F10 melanoma cell line were studied and the uptake was observed in melanoma cell line. The biodistribution study in white and black mice has been performed.