# Presentation: 049866

## 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
- 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

## 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: 99mTc -DMSA complex (dimercaptosuccinic acid)

## 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

## 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

## 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

## 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