The Role of Technetium in Nuclear Medicine

1. 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

2. Production of technetium-99m • Technetium was first predicted by the russian chemist Mendeleev, first isolated by Segré and Perrier in 1938 • 99mTc 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 99Mo elutes the soluble 99mTc as [TcO4]- technetium-99 generator Tucker & Richards

3. 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

4. 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

5. Sestamibi

6. 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

7. 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

8. Agents for renal function Most important: 99mTc -DMSAcomplex (dimercaptosuccinic acid)

9. 99mTc -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

10. Agents for renal function Most recent and now widely used anionic kidney imaging agent: 99mTcO-mercaptoacetyltriglycine Free carboxylic acid group is believed to be necessary for efficient renal excretion

11. 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 N2S2 diaminedithiol -forms a stable, neutral, square pyramidal Tc=O species with 99mTc-[TcO4]- -the uptake of these antibodies is quite slow, it can take up to 20 hours

12. Recent development Very recently, there have been reports of the preparation of the 94Tc isotope by irradiation of 94Mo in a cyclotron 94mTc as well as 94gTc are positron emitters and could be also used for taking PET images But: Though the characteristics of 94Tc 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