ORGANIC-RADIOPHARMACEUTICAL CHEMISTRY

Specific Foundation / Core

Upon completion of the teaching and examination, students will have learned the application of new trends in the pharmacochemical aspect of drug design and the successful treatment of pathological conditions (incurable or poorly treated diseases, treatment of toxic chemicals). Students will have learned to use modern pharmacochemical methods. They will have learned about the chemical structure-characteristics of chemical groups in relation to biological action. They will have learned the relationship between physicochemical properties and biological activity. Further, students will have learned free radical pharmacochemistry, the role of oxygen in life, free radical reactions in biological systems, reactive forms of oxygen, and the mechanism by which free radicals attack lipids, proteins, and DNA. Students will have learned the normal defense mechanisms against free radicals and the interpretation of the phenomenon of oxidative stress. They will also have learned about the structure, function and physiological role of the blood-brain barrier in relation to the action of drugs. Further, students will have learned the properties and methods of applying ionizing radiation in radiopharmacy. Students will have learned the nuclear properties of radionuclides by applying them to radiopharmaceuticals. Students will have learned the methods of labeling classic radionuclides. In addition: they will have learned the design and mechanism of action of the main radiopharmaceuticals used today as well as their applications in Nuclear Medicine. Finally, they will have learned the methods of radiochemical control of radiopharmaceuticals. All these learning outcomes are necessary qualifications required for Pharmacists to work.

This course presents some modern aspects in the broad field of bioactive molecules (drugs, poisons) and the molecular approach to pathologic conditions, aiming to a rational confrontation of them through drug design. The effect of the chemical characteristic groups on activity and toxicity of drug molecules is studied and an approximation in physicochemical properties/chemical structure/activity relationships is performed. Further topics are: Pharmacochemistry of free radicals. Role of oxygen in aerobic life, free radical reactions in biological systems. Reactive oxygen species. Mechanisms of radical attack on lipids, proteins, DNA. Defence of the body against radical offence, the involved mechanisms. Structure, function of blood brain barrier and drug permeability. Radioactivity: Radioactive decay, α, β-, β+, particle emissions, electron capture, γ ray emission, isomeric transition, internal conversion, Auger electrons. Law of radioactivity, Half-life, Successive decay equations, transient and secular equilibrium. Interaction of radiation with matter: ionization, bremsstrahlung, annihilation, photoelectric effect, Compton scattering, pair production. Radiolysis of water, effect of radiation on macromolecules, DNA strand breaks, oxygen effect. Radionuclide generator: Principles of a generator. 99Mo/99mTc generator. Yield of 99mTc. Radionuclide, radiochemical and chemical purity of 99Μο/99mTc generator eluate. Labeled compounds: Radionuclide, radiochemical and chemical purity of labeled compounds. Methods of radiochemical yield calculation (radiochromatography). Radiopharmaceuticals: general principles, diagnostic and therapeutic radiopharmaceuticals. Properties of 99mTc. Chemistry of 99mTc. Labeling with 99mTc (Labeling with reduced 99mTc, Formation of 99mTc-complexes by ligands exchange, reducing agents). Techentium(V), oxo core, isomerism. Methods of radioiodination of proteins (iodine chloride, iodogen, chloramin-T, enzymatic methods) Radiopharmaceuticals of 99mTc and other radionuclides (preparation, clinical applications, pharmacokinetic data). Sodium pertechnetate, technetium-sulfur colloid, technetium-human albumin macroaggregates, technetium-DTPA, technetiumglucoheptate, technetium-succimer, trivalent and pentavalent, technetiummethylendiphosphonate, technetium-iminodiacetic acid derivatives, technetiumhexamethylene amine oxime, technetium- ethyl cysteinate dimmer, technetiummercaptoacetyltriglycine, technetium-hexacis(2-methoxy-isobutyl-isonitrile). [188Re]- rhenium-(hydroxiethylidine diphosphonate). [111In]-Indium-tris (oxine). [123/131Ι]- Sodium Iodide, [123/131Ι]-metaiodobenzyl-guanidine. [18F]-2-fluorodeoxyglucose. Thallium-201. Labeling monoclonal antibodies-advantages and disadvantages. Direct labeling of mAbs with radio-iodine and technetium. Red blood cell labeling with technetium and indium.

11-11-2020