Preparation of Some Radiopharmaceuticals as Radionuclide Carriers for Tumor Imaging

This thesis is divided into four main parts: Part I: Design, Development and Optimization of M P D Microemulsion Systems. This part describes the procedures of M P D microemulsion (M P D M E) systems preparation using water titration technique and M D P solution (M P D S) preparation. Characterization and optimization of M P D M E formulae were performed. A 3¹2² full factorial design using Design-Expert® software was adopted to investigate the effect of different system parameters on M E characteristics and to identify the optimum system. The morphology of the optimum M P D M E system using transmission electron microscopy (T E M) was performed. The compatibility assessment of optimum M P D M E and M P D S with different injectable diluents was evaluated. In addition, in vitro hemolytic studies and in vivo histopathological examination were performed, using male albino rabbits, to examine the hemolytic and possible irritation potentials of optimum M P D M E and M P D S, respectively. The cytotoxicity of optimum M P D M E and M P D S in Michigan Cancer Foundation 7 (M C F-7) breast cancer cell line was conducted compared to tamoxifen. The obtained results showed that the phase diagrams containing (Tween 20, Tween 40 and Tween 80) as a surfactant, ethanol as a co surfactant with ratios (1:1 and 1:2), oil (I P M) and water were developed and the A U Cs representing the clear zones were calculated. A full 3¹2² factorial design was adopted in preparing the optimum M P D M E system (M P D M E 1) that showed small P S, small P D I, high Z P and spherical droplets. T E M photograph showed that the particles were finely distributed, spherical in shape and had a uniform droplet size distribution. M P D M E 1 did not show hemolytic activity (H D % ≤ 5%) even at the highest tested concentration while the hemolytic activity of M P D S increased as the drug concentration increased. The in vivo histopathological studies confirmed the non irritant nature and safety of M P D M E 1 in the study animals. The cytotoxicity of M P D M E 1 in M C F-7 cells was superior to M P D S and tamoxifen.Part II: Molecular Modeling, Molecular Docking and Radiolabeling of Optimum M P D Microemulsion and M P D Solution Systems Using Iodine-125 This part describes the procedures to evaluate A 10, M P D and ¹²⁵I-M P D as H D A C 8 inhibitors by molecular docking. It describes the procedures of radiolabeling of M P D M E 1, M P D S and placebo with ¹²⁵I via direct electrophilic substitution reaction using Chloramine-T (C A T) as an oxidizing agent Part III: Molecular Modeling, Molecular Docking and Radiolabeling of Optimum M P D Microemulsion and M P D Solution Systems Using Technetium 99 m. This part describes the evaluation of binding affinity of M P D as well as ^99mTc-M P D with the DNA using molecular docking. Part Vi: Biological Evaluation of the Labeled Systems