Radiopharmaceuticals for nuclear medicine

Medical University of Lodz

Dr Janusz Kapuściński 1

2

A branch of medicine and medicine imaging, that

for diagnostics and theraphy uses open sources

of radiation administred to patients.

Nuclear Medicine

Radioactive substances are administered to

patients and the radiation emitted is detected.

Nuclear Medicine

NM is a part of

molecular imaging -

it produces images

that reflect biological

processes that take

place at the cellular

and subcellular level.

Nuclear Medicine

Nuclear medicine procedures use

radiopharmaceuticals – pharmaceuticals

labeled with radionuclides.

Nuclear Medicine

A radiopharmaceutical consists of two

functional components:

- radioactive

- non-radioactive.

The radioactive component enables detection

of the radiopharmaceutical. It is a radionuclide

with appropriate physical properties.

The non-radioactive component is a molecule

with appropriate pharmaco-kinetics. It is

accumulated in the target organ and it

determines biological behaviour of the

radiopharmaceutical in the body.

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Radiopharmaceuticals

Some nuclides can be used "as is".

- radioactive iodine is absorbed directly by

thyroid gland.

- radioactive thallium is absorbed directly

by heart muscle and can be used to

investigate whether parts of heart are

functioning normally.

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Radiopharmaceuticals

Most radioactive nuclides must be bound with

a carrier molecule which enables them to bind

to cells or processes we want to image.

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Radiopharmaceuticals

Carrier molecule has an affinity for a certain

type of cell or receptor.

These molecules carry 99mTc or other

radionuclides to the sites in the body which

we want to image.

Properties of ideal diagnostic RF:

o pure gamma emitter

o 100 < gamma energy < 250 keV

o short effective half-life

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Radiopharmaceuticals

o high target : non-target ratio

o chemical reactivity

o inexpensive, easily available

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maximum efficacy in diagnosis

minimum radiation dose.

Properties of ideal diagnostic RF:

Radiopharmaceuticals

Main advantages of Technetium-99m

as radioisotope label

o Short half-life (6.02 hours - low radiation dose)

o Pure gamma radiation (absence of alfa and beta emission - low radio toxicity)

o Energy of gamma quantum – 140 keV (convenient for detection)

o Reactive (chemical bounds with various compounds)

o Inexpensive, easily and instantly available (Mo/Tc radionuclide generator)

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Many radiopharmaceuticals use technetium

(99mTc) as a radiotracer.

Different radiopharmaceuticals based on 99mTc

are used for imaging and functional studies of

brain, myocardium, thyroid, lungs, liver,

kidneys,, gallbladder, skeleton, blood and

tumors.

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Radiopharmaceuticals

99mTc is a radioisotope

used in over 85% of

nuclear medicine

diagnostic procedures.

Technetium-99m

Since 99mTc has a half-life

of only 6 hours, it is

generated on a just-in-

time basis from its parent

radioisotope

molybdenum-99, which

has a half-life of 66 hours.

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99Mo/99mTc radionuclide generator

Generator is a lead-

shielded column

containing a resin to

which 99Mo is attached.

99Mo decays to produce

the short-lived 99mTc.

To obtain 99mTc,

physiological saline (the

eluent) is injected into

the top of the column. 14

The eluent is passed

through the column and

NaTcO4 - sodium

pertechnetate, (the

daughter of 99Mo-

decay), is eluted.

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99Mo/99mTc radionuclide generator

The pertechnetate is

collected in a shielded,

evacuated sterile vial

and calibrated prior to

use.

It is referred to as the

eluate.

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99Mo/99mTc radionuclide generator

99mTc obtained from

Mo/Tc generator is in +7

oxidation state and does

not form complexes.

The majority of 99mTc

compounds employ

stannous reduction

method.

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Technetium labelling

A reducing agent is

therefore required to

convert the 99mTc into a

form capable of binding

to chelating agents.

In redox reactions TcO4-

is reduced to Tc4+ by

stannous ion (Sn2+).

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Technetium labelling

If a vial contains an

agent capable of

chelating 99mTc, the

reaction occurs almost

immediately.

The pharmaceutical

agent is thus labelled

with the radionuclide.

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Technetium labelling

Technetium labelling

Chemistry of technetium allows it to form a

stable complex with a relatively wide range of

chemical chelation agents.

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Ulrich Abram, Roger Alberto: Technetium and rhenium - coordination chemistry and nuclear medical applications. J. Braz. Chem. Soc. 2006; vol.17 no.8

Kits for labeling with Tc-99m

Most widely used kits:

o MIBI (myocardial perfusion scintigraphy)

o MDP or HEDP (skeleton scintigraphy)

o DTPA (renoscintigraphy – renal function)

o EC or MAG3 (renoscintigraphy – renal function)

o MAA (perfusion lung scintigraphy)

o IDA derivatives (bilary ducts scintigraphy)

o sulfur colloid (liver and spleen scintigraphy).

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Typically a radiopharmacy has a specialized

lab to manufacture, label and store each

different radioactive drug.

Radiopharmacy

For preparation of sterile

radiopharmaceuticals the

working area should comply

with appropriate environmental

requirements.

This may be achieved by the

provision of a workstation with

a laminar flow of HEPA-filtered

Grade A air.

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Radiopharmaceuticals preparation

In order to minimize the radiation risk to the personnel the work area must be adequately shielded.

The lead surfaces of the shielding must be covered (stainless steel).

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Radiopharmaceuticals preparation