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Pc the role of technetium in nuclear medicine
 

Pc the role of technetium in nuclear medicine

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    Pc the role of technetium in nuclear medicine Pc the role of technetium in nuclear medicine Presentation Transcript

    • The Role of Technetium in Nuclear Medicine
      • Definition of Nuclear Medicine:
      • branch of medicine and medical imaging that uses radioactive substances in therapy and diagnosis
      • - gamma rays (  SPECT)
      • positrons (  PET)
      • Tracer principle: George de Hevesy (Nobel Prize in Chemistry in 1943)
      • - radionuclide is typically given in very low doses; it won’t have any pharmaceutical interaction within the body
    • Production of technetium-99m
      • Technetium was first predicted by the russian chemist Mendeleev, first isolated by Segré and Perrier in 1938
      • 99m Tc is used for medical imaging due to its nearly ideal nuclear characteristics of a 6 hours half-life and gamma-ray emission energy of 141 keV
      • Technetium-99 generator developed at Brookhaven
      • consists of a column filled with acid alumnia, in which molybdenum-99 is adsorbed
      • pulling normal saline solution through the column of immobilized 99 Mo elutes the soluble 99m Tc as [TcO4] -
      technetium-99 generator Tucker & Richards
    • Myocardial imaging agents
      • First approach: lipophilic unipositively charged complexes should accumulate in heart tissue via the Na/K-ATPase mechanism as K + mimics
      • But:
      • first complexes were reduced in vitro to a neutral Tc2 + complex which had lost the positive charge
      • accumulated in the liver
    • Sestamibi
      • Myocardial perfusion agent
      • - produced as Cardiolite by DuPont
      • Mechanism of uptake:
      • Cations like Sestamibi accumulate via diffusion and electrostatic binding due to a high mitochondrial membrane potential
      • - the lipophilicity of the complex is known to be important for uptake into the heart
      • important for the cardiac stress test  one radionuclide for rest test, one for stress test
      • Also used for parathyroid imaging:
      • Sestamibi will be taken up by an adenoma of the thyroid
    • Sestamibi
    • Cerebral blood flow agents
      • Most important requirement:
      • Agent must be able to pass the blood-brain barrier
      • complexes must therefore be lipophilic and have an overall neutral charge
    • Ceretec
      • was selected from more than 100 structural variants for its optimal biodistribution characteristics
      • different sorts of brain damage can be detected with Ceretec like strokes, dementia, psychoses, epilepsy or carotid artery diseases
      •  perfusion defects can be seen with SPECT earlier
      hexamethylpropyleneamineoxime
    • Agents for renal function Most important: 99m Tc -DMSA complex (dimercaptosuccinic acid)
    • 99m Tc -DMSA Mechanism of uptake: Accumulates in the kidneys and specially localizes in the proximal convoluted tubule In the proximal convoluted tubule most of the water and salts are reabsorbed  Shows ability of the kidneys to filter the blood Nephron
    • Agents for renal function Most recent and now widely used anionic kidney imaging agent: 99m TcO-mercaptoacetyltriglycine Free carboxylic acid group is believed to be necessary for efficient renal excretion
    • Monoclonal antibodies or antibody fragments Monoclonal antibodies or their fragments are potentially ideal vehicles to carry radioisotopes to specific sites within the body But: radiolabel has to be inserted without affecting the binding site! elegant route to binding the antibody to the Tc is via a thiolactone which generates an N 2 S 2 diaminedithiol -forms a stable, neutral, square pyramidal Tc=O species with 99m Tc-[TcO4] - -the uptake of these antibodies is quite slow, it can take up to 20 hours
    • Recent development Very recently, there have been reports of the preparation of the 94 Tc isotope by irradiation of 94 Mo in a cyclotron 94m Tc as well as 94g Tc are positron emitters and could be also used for taking PET images But: Though the characteristics of 94 Tc are really good, you still need an expensive cyclotron to produce it; that limits its usage Future role -Monoclonal antibodies as tracers for all different kinds of tumors -SPECT/CT good method for better planning of surgery