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

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Production of technetium-99mTechnetium 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

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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

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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

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Sestamibi

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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

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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

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Agents for renal function

Most important: 99mTc -DMSA complex (dimercaptosuccinic acid)

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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

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Agents for renal functionMost recent and now widely used anionic kidney imaging agent:

99mTcO-mercaptoacetyltriglycine

Free carboxylic acid group is believed to be necessary for efficient renal excretion

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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

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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

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