الفهرس 
INTRODUCTION AND OBJECT OF INVESTIGATION
Types of RadiopharmaceuticalsOnly 14 pages are availabe for public view
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Abstract
Development of new brain radiopharmaceuticals for SPECT imaging has progressed rapidly in recent years. The SPECT alone or in combination with PET and/or functional magnetic resonance imaging (fMRI) is used in studying human cognition, imaging of neuroreceptor systems, aiding in diagnosis or assessment of progression of neurologic disorders and following up responses to psychiatric treatments. SPECT, in comparison with PET, has an advantage of being widely available worldwide. SPECT was originally developed for clinical use, and the subsequent preclinical adaptation of the imaging modality allowed for longitudinal molecular imaging of small laboratory animals. The proper radiopharmaceutical used for brain imaging procedures should be able to bind with high affinity to the receptors and reach its target by passing through the BBB. In addition, it should have a short half-life time and suitable photon energy within the range of the used gamma camera.
The aim of this thesis is to develop potential selective radiopharmaceuticals for the non-invasive brain imaging. TZN, QTP and CBP (three drugs that have the ability to cross BBB and bind to the target receptors) were successfully radiolabeled and their biodistribution in mice were studied and confirmed via imaging. This investigation was divided mainly into three main chapters:
Chapter (I): Introduction and Object of Investigation This includes a brief accounts on radioactivity and its types, radionuclides and its decay processes, radiopharmaceuticals and its types, characteristics of ideal radiopharmaceuticals, quality control of radiopharmaceuticals, chemistry and radiochemistry of iodine, radioactive waste and how to treat it, nuclear medicine, human brain, brain imaging in nuclear medicine and radiopharmaceuticals used for it, TZN, QTP, CBP and literature surveys on them. It also includes the aim of this work.
Chapter (II): Materials and Methods of Investigation
This chapter includes:
Detailed information concerning the materials, the equipment, the animals and the buffers used in this study.
The procedure of electrophilic radioiodination of TZN, QTP and CBP and how to determine the radiochemical yield.
The procedure of obtaining the optimum conditions of radiolabeling of the drugs.
The procedure of determination of radiochemical purity and partition coefficient of the radiolabeled drugs. The procedure of biodistribution studies and in vivo imaging with the radiolabeled drugs in mice.
Chapter (III): Results and Discussion
This chapter deals with the radiolabeling processes of TZN, QTP and CBP with iodine-125 by electrophilic substitution reaction and select the optimum conditions required to give the maximum radiochemical yield of 125I-TZN, 125I-QTP and 125I-CBP. The radiolabeled drugs were biologically evaluated in normal mice, to elucidate its specific binding to the brain receptors. These results showed that:
125I-TZN was obtained by using 100 μg TZN with iodine-125 in neutral medium pH = 7 using 50 μg CAT as an oxidizing agent. The reaction mixture was incubated at room temperature for 15 min. The obtained radiochemical yield was 92.8 % ± 0.1.
The radiolabeling of QTP was done by adding 100 μg QTP to 50 μg CAT as an oxidizing agent and then the radioactive iodine was added at pH 2. The reaction mixture was heated at 60 ºC for 30 min. The radiochemical yield reached 94.5 % ± 1.5.
100 μg CBP was successfully radiolabeled with iodine-125 with a maximum radiochemical yield of 91.7 % ± 0.6 by direct labeling technique by using 150 μg CAT in acidic medium (pH = 2) at 70 oC for 30 min. The stability of 125I-TZN, 125I-QTP and 125I-CBP were studied and the results were up to 2, 4 and 4 h, respectively, without detection of any by-products in the reaction mixture.
The partition coefficient values were 2.21 ± 0.02, 1.97 ± 0.01 and 1.76 ± 0.03 for 125I-TZN, 125I-QTP and 125I-CBP, respectively, showing that they are lipophilic compounds, so they have a rapid permeation through the BBB.
The biodistribution profile of the drugs in normal Swiss albino mice via intravenous route was investigated at different time intervals and showed that the maximum uptake of radioiodinated TZN and QTP by the brain of mice was 5.2 % and 3.5 %, respectively, at 120 min post injection while the maximum uptake of radioiodinated CBP was 2.9 % at 240 min post injection.
The SPECT imaging confirmed the results of biodistribution studies where the maximum uptake of radioiodinated TZN and QTP by the brain of mice was 8.0 % and 10.9 %, respectively, at 120 min post injection while the maximum uptake of radioiodinated CBP was 12.4 % at 240 min post injection.