Nuclear Medicine

There are three methods through which artificial radionuclides are form:

1. Irradiation of a stable nuclide in a reactor with thermal neutrons, i.e. reactor produced (e.g. Tc-99m)
2. Fission of heavier nuclides to produce a radioactive substance, i.e. fission produced (e.g. Ba-141 and Kr-91 from the fission of U-235)
3. Irradiation of a nuclide in a cyclotron or accelerator, i.e. cyclotron produced (e.g. F-18)

The two most common radionuclides are Tc-99m and F-18. Tc-99m is produced from Mo-99 and is used in nuclear medicine. Mo-99 is reactor produced from Mo-98. F-18 is cyclotron produced and is used widely in Positron Emission Tomography.

Fluorine-18 Deoxyglucose

This substance is commonly used in PET to demonstrate uptake of glucose by cells. It is manufactured by replacing a hydroxyl group in glucose with a cyclotron-produced F-18 molecule. It has a half-life of 110 minutes and can be used to demonstrate cellular metabolism.

Decay

Reactor-produced radionuclides decay by beta minus decay. The radionuclides are produced through reaction of a stable nuclide with thermal neutrons. This means they have an excess of neutrons. They lose this neutron and gain a proton through beta minus decay.

When radionuclides are cyclotron produced, they are bombarded with protons. This means they have an excess of protons, which they lose through beta plus decay, emitting a positron.

Why is the Mo-99 to Tc-99m generator so popular in nuclear medicine?

• Mo-99 has a long half life of 67 hours, meaning the generator can be manufactured interstate or internationally and then shipped to the hospital for clinical use
• Generator can last a long time at the hospital, ranging between 1 to 2 weeks
• Constant production of Tc-99m, meaning it can be milked for clinical use
• Tc-99m can be milked several times a day for different clinical applications
• Tc-99m produces gamma rays which have an energy appropriate for detection by gamma cameras (140keV)
• Tc-99m has a long enough half life for the duration of examination but not too much to pose radiation damage to patient or personnel

How do cyclotrons produce artificial radionuclides?

A cyclotron consists of two electrical 'dees' in a vacuum chamber, which sits in between two poles of a large magnet. The magnet functions to create a perpendicular magnetic field. An ion is then dropped into the centre of the cyclotron and a high voltage is applied across the dees of the cyclotron. The electrical potential of the dees causes the ion to accelerate to the dee of opposite charge. The dees then alternate, causing the ions to accelerate in the opposite direction. With constantly alternating voltages, the ion continues to accelerate between the dees. A strong magnetic field bends the particle motion into a circular path.

As the dees change in energy and the ion takes a larger circular path around the cyclotron, it continues until it gains maximum energy. It then spirals out of the chamber and crashes into the target material to produce a radioisotope. This isotope is then 'proton-rich'.

F-18 is the most common cyclotron-produced radioisotope, produced from the bombardment of O-16 with He-3 (charged particle).

Characteristics of Radiopharmaceuticals

• Pure gamma emitter
• Gamma energy between 100 and 250keV
• Effective half life which is 1.5 times the duration of the examination
• A high target to non-target ratio
• Minimal dose to the patient and nuclear medicine personnel
• Patient safety
• Suitable chemical reactivity
• Inexpensive and readily available
• Simple preparation and quality control, if manufactured in house

The one radiopharmaceutical that comes close to meeting these criteria is Tc-99m. It is a nearly pure gamma photon emitter which are of 140keV. It has a half-life of 6 hours.

NB: If the energy of the gamma rays is lower than 100keV, it will produce light in the scintillation crystal but this light will be absorbed by the crystal itself and will not reach the PMTs. If the energy of the gamma rays is higher than 250keV, it will pass straight through the detector.

Half-Life

Physical half-life is the time it takes for the activity of the radionuclide to decay to half its original value. Biological half-life is the time it takes for half the radionuclide to exit the body, which may change depending on the patient and amount etc. The physical half-life does not change. The effective half-life is a combination of the two, allowing us to determine patient dose. It is equal to the product of the physical and biological half-lives divided by the sum of the physical and biological half-lives.

Radiation Detection

Radiation detection involves characterising the source based on its:

• Energy
• Activity
• Nature

The detector must be designed to suit the source based on intrinsic efficiency, dead time and energy discrimination. Dead time is the time after each recorded event where the detector can not process another event, because it is processing the previous event. It is non-paralyzable, where the non-recorded event is lost, or paralyzable, where the non-recorded event restarts the dead time.

Gas Filled Detectors

Gas filled detectors are chambers full of gas. Incoming radiation interacts with the gas through ionisation to form some ion pairs. Positive ions migrate to the negative plate and negative ions migrate to the positive plate, thereby producing an electric current. The more radiation that is incoming, the more ionisations and the greater the electric signal produced. Thus, the electric current is proportional to radiation intensity.

When a low voltage is applied across the detector, some ion pairs will be produced however they will more likely recombine that migrate to opposite plates. When a high voltage is applied, the particles have increased acceleration to opposite plates and the electrical signal is high.

There are three main types of gas filled detectors used in nuclear medicine.

Ionisation chambers

• Fairly insensitive
• Do not count individual events but accumulate all data into one electrical current
• Current is dependent on the number of events and energies of the events
• Used to measure radiation exposure from diagnostic x-ray machines and dose calibration in nuclear medicine

Proportional counters

• Rarely used in nuclear medicine

Geiger-Muller counters

• Very sensitive
• Can count individual events
• Unable to count energies of events, however
• Mainly used as contamination monitors in nuclear medicine

GAMMA CAMERAS

Absorption collimators are placed before the sodium iodine crystal crystal in the gamma camera to absorb scattered gamma photons. There are four types of collimator:

• Parallel hole
• Pin hole
• Converging
• Diverging

As the distance between the patient and the collimator increases, the more scatter photons let through increases because the divergence of the collimator decreases. 

A gamma camera consists of the collimator, sodium iodide crystal, photomultiplier tube array, pulse height analyser, position-logic circuit and computer for display. Gamma rays are emitted by the patient and deposit energy in the scintillation crystal, which is given off as a burst of light. The light is detected by the PMT and an electron is ejected from the PMT. Within the PMT are a series of diodes held at increasing voltage. The electron is accelerated to the first diode, where it ejects 3-4 electrons. All these electrons are accelerated to the next diode, each ejecting 3-4 electrons. This continues until nearly a million electrons are produced, which give off a voltage pulse proportional to light intensity detected initially. The voltage pulses of all PMTs are summed and a window of voltage pulses is accepted, with anything below being rejected as scatter. Position-Logic circuits determine the x and y coordinates of the event in the crystal and thus in the patient, while the pulse height analyser determines the energy of the incident gamma ray.

Scatter Removal

Scatter radiation is produced when the gamma photon excites an electron to a higher energy state, which then falls back down and gives off a scatter photon which is lower energy and moves off in a different direction to the incident gamma photon.

There are two methods through which scatter is removed using a gamma camera. Absorption collimators, ineffective but necessary, are used to remove scatter before it reaches the scintillation crystal. The pulse height analyser also removes scatter radiation based on the sum of the voltage pulses, the z pulse. The pulse height analyser selects a window of pulses it will accept. Anything below this window, i.e. scattered events, will be disregarded and not contribute to diagnosis.

Pulse Height Analyser

A pulse height analyser analyses the sum all voltage pulses from the photomultiplier tubes, i.e. the z pulse, which is proportional to the incident gamma photon energy. The pulse height analyser selects a window or 'energy range'. It decides to accept pulses (true events) within this range and exclude pulses (scatter events) which like below this range. If the pulses are accepted, they are stored in a computer and displayed on a monitor in positions determined by x and y.

PET

PET stands for positron emission tomography and is a functional imaging modality within nuclear medicine. The machine itself consists of 360 degrees of detectors, each covered by bismuth germinate crystals, which have a higher density of NaI crystals to compensate for higher photon energies. PET, unlike in planar imaging in nuclear medicine, uses positron emitting radionuclides. This means the artificial radionuclide must decay by beta positive decay, in order to release a positron. Within the patient, this positron then travels a few mm before combining with an electron in pair annihilation. The product of this annihilation is two 511keV photons which speed of 180 degrees from each other. They are then coincidentally detected by completely opposite detectors. The direction of these photons is termed the line of response.

F-18 is the most common radionuclide used in PET, and is produced from the bombardment of O-16 with He-3 in a cyclotron. It has a half-life of 110 minutes. However, PET machines are expensive and because of the short half-life of F-18, production must occur near the hospital, e.g. at the SAMRI beside the nRAH.

Advantages over SPECT: no need for collimation as scatter removal is electronic, deeming it more sensitive, and attenuation correction is easier

PET/CT

A recent development in nuclear medicine involves the combination of PET and CT in one scan. The patient firstly passes through a CT machine, and an image is formed based on the detected x-ray intensity after transmission through the patient. The patient then continues through a PET scanner, which is based on coincident detection of gamma rays resulting from pair annihilation of positron and electron. The two scans can then be fused to form an image of functional anatomy. Areas of high activity in PET can be colour coded on the CT image.

Benefit: CT corrects for attenuation in PET.

SPECT

SPECT stands for single photon emission computed tomography. It utilises gamma cameras which take various 2D images from various angles, which are then tomographically reconstructed into 3D images. In SPECT, a gamma emitting radionuclide is administered and the gamma rays are detected using NaI crystals and PMTs. The radionuclides are either reactor or fission produced, e.g. Tc-99m. Once all the data is acquired, filtered back projection is undergone.

The data is back projected onto a matrix. The data is pushed back along the path it took in space and the brightness is summed and pixel values are added up and normalised. The brighter the back projection stripe, the greater the x-ray attenuation. Back projection produces a star effect, which is eliminated using a convolution filter, deeming it filtered back projection. 

Examples of SPECT include myocardial perfusion imaging and 3D gated blood pool studies.