Nuclear Medicine

Learning Objectives

• Understand the basic physical and engineering principles of nuclear medicine.
• Be able to discuss the various technologies implemented in nuclear medicine.
• Be aware of the clinical implementation of nuclear medicine

Nuclear Medicine Imaging

Is functional molecular imaging, which takes advantage of molecular interactions in tissues and organs. Pharmaceuticals tagged with radionuclides are injected into patients. Radiopharmaceutical accumulates in the organ of interest. Then the imaging is performed and the pathway of the pharmaceutical is measured.

Compared to an X-ray, there are some fundamental differences:

• Nuclear medicine measures function not the structure of the anatomy
• Image contrast is due to the uptake not due to the attenuation
• Radiation source is inside the body and not the outside
• Radiation emission position and detection unknown
• Radiation emitted before, after and during imaging

Alpha, beta and gamma rays are involved in nuclear medicine. Alpha rays get stopped by paper, beta get stop by aluminium and mostly get stopped by lead.

What is radioactivity?

Radioactive materials are unstable and have insufficient binding energy to hold constituent particles together. With time the nucleus changes and the number of protons/neutrons change. These changes result in the emission of radiation. Decay probability is characteristic of the nucleus. Radioactivity is measured in Becquerels (disintegrations per second).

Half-life is the time required for half the atoms to decay. The activity is also reduced by half.

Radioactive Decay

A = A₀e^-λt

Where λ is the decay constant

If we have 100 MBq of Tc-99m, how much activity do we have after two hours given that the decay constant is λ = 3.21 x 10^-5 S^-1?

A = A₀e^-λt
A = 100e^{-3.21 x 10-5 x 7200}
A = 79.36 MBq

Radionuclides

The ideal characteristics of the radio-labeled chelator:

• X-ray or γ-ray type of radiation
• 120-180 keV of photon energy 79 keV (²⁰¹TI) to 360 keV (¹³¹I)
• Half-life depends on the uptake rate, and is normally hours only duration of hour long it is required.

Generation of Radionuclide

There are two main ways of producing radionuclides in hospitals, either through direct (nuclear reactor or cyclotron) or indirect (generators) means.

Many parent radionuclides go to a ‘metastable’ state through beta or alpha emission. Metastable daughter loses excess energy as a gamma photon to revert to ground state. Most common radionuclide in Nuclear Medicine is a metastable isotope Tc-99m (6.01 hour decay) which is the beta-emission ‘daughter’ of Mo-99 (66 hour decay).

A generator has an eluate (collection) vial at low pressure containing saline. A pressure difference draws saline into a column containing Mo-99 on Alumina beads. The saline washes off Tc-99m into eluate vial. Sodium Pertechnetate (NaTc0₄) ends up in the eluate. There is lead shielding all around the generator to protect the technicians. Special calibration equipment is used to determine whether the strength of the radioactivity is correct.

Which Radionuclide?

The organ/tissue of interest will determine the choice of radiopharmaceutical to be used.

Radionuclide Detection

Nuclear medicine scanners have advanced tremendously since their invention in 1950. A gamma camera is suspended above a patient obtaining a 2D image from a 3D distribution of radioactivity.

Scintillation Crystal

The scintillation crystal absorbs energy from incident gamma radiation giving out corresponding photons so we can detect the intensity of the radiation as light. Key properties of a scintillation crystal are:

• Attenuation coefficient
• Scintillation efficiency
• Speed
• Colour of light emission
• Physical properties
• Linear conversion of radiation energy into light energy.

Typical scintillator crystals are NaI(TI)

Photomultiplier Tube

The incident light photon from the scintillation crystals travels into the photomultiplier tube forcing electron emission from photocathode. The electron is focused onto first dynode which is at a higher potential than the focusing electrode causing the electrons to gain kinetic energy. The kinetic energy of the electrons is absorbed further in the dynode, freeing even more electrons in the process. This is repeated over 10-15 dynodes each at a higher potential. The pulse of charge is collected at the anode.

Photomultiplier tube size is 50 - 75mm

Collimators

Gamma rays are emitted in all directions from the patient, and in order to determine their location of origin a collimator is used. A collimator can be thought of a very tiny bunch of straws, and they have many different designs including parallel hole (most common), pin-hole, converging and fan-beam. The different designs stop the scattered photons in different ways depending on what imaging is required and many different factors have to be taken into account:

• Septal thickness (s): Photon Energy
• Hole length and width: Sensitivity vs Resolution, position of the source, type of scan and activity in the patient.
• Type of scan: Static or Dynamic
• Required resolution

However a collimator reduces the sensitivity of a detector system. The higher the resolution, the lower the sensitivity as more photons are absorbed by the collimator. Also collimators cannot avoid picking up scattered photons but these effects can be reduced by using energy discrimination of pulse height analysis. Without collimators intrinsic position calculation is ~3mm Full Width at Half Maximum (FWHM).

$ Energy \ Resolution = \frac{FWHM \ \times \ 100}{Peak \ Energy}\% $

Note: FWHM is full width of a peak at half its height.

Alternative Technologies

Scintillation detectors are bulky and have a relatively poor energy resolution. Recently some new Nuclear Medicine systems uses solid state semi-conductor detectors instead. These have a superior energy resolution, smaller and slim, costly are made up of substances such as Cadmium Zinc Telluride.

Avalanche Photodiode is an alternative to the photomultiplier tube, with a semiconductor detector sensitive to light photons. These are smaller, more compact, have a high quantum efficiency but are noisy and have a low timing resolution.

Image formation

X and Y position signals are converted to digital form with analogue to digital convertor. The address memory location is incremented. The final image is then displayed on a standard computer display. There are many different parameters which determine the characteristics of the output image:

• Energy e.g. 140 keV (+/- 10%)
• Pixel size = FWHM / (2 or 3)
• Matrix size = Detector size / Pixel size. Dynamic Imaging ( 64 x 64, 128 x 128 ) and Static Imaging ( > 256 x 256 )
• Pixel Depth 2⁸8 = 255 ~~~~ There are two main types of image acquisition:

1. Static Acquisition thyroid bone lung

The distribution of the radiopharmaceutical is fixed over the imaging period. The gamma camera is positioned over the area of interest for a fixed time and counts are accumulated. Multiple images from different angles can be acquired (e.g. anterior, posterior, oblique)

2. Dynamic Acquisition renogram GI bleed

Consecutive images are acquired over a period of time. The camera is in a fixed position allowing visualisation of the changing distribution of the radiopharmaceutical in the organ of interest.

Tomographic imaging

There are lots of limitations with planar images as they represent a 3D distribution of activity. Depth information does not exist and structures at different depths are superimposed. Loss of contrast in plane of interest is due to underlying and overlying structures. Tomographic images find a cross-section and can be more useful and prevent some of these limitations.

Single Photon Emission Computed Tomography SPECT

A set of angular projections of the activity distribution within the patient are acquired by rotating the gamma camera(s) around the patient. Images are reconstructed using filter back projection and iterative reconstruction. Some parameters that affect SPECT acquisitions include:

• Rotation speed (acquisition time at each angle)
• Number of angular samples
• Pixel size
• Rotation mode: step and shoot or continuous

Position Emission Tomography PET

This uses positron emission radionuclides (e.g. F-18, O-15, C-11). When these radionuclides interact with tissue they emit two 511 keV gamma rays. These gamma rays are emitted at 180° to each other and are detected in coincidence, improving the sensitivity. Just to compare a collimated single photon system has an absolute sensitivity of ~0.05% compared to ~0.5 - 5% of PET. The main application of PET is in oncology (study and treatment of tumours).

NM imaging limitations

Here is a list of limitations of nuclear medicine, with the main ones highlighted in bold:

• Scanner & Radiopharmaceutical
• Resolution
• Sensitivity
• Radiation Protection issues (before, during and after process)
• Patient motion
• Lengthy scans from 15mins - 1 hour
• Attenuation correction
• Localisation

Attenuation Correction

Two lesions with identical uptake but in different locations, will not have the same contrast. As the positrons emitting from one lesion will have to further than the other losing more energy and getting absorbed in the process. In order to resolve this a hybrid system is used, where SPECT/PET is used in combination with a low-dose CT. The information from SPECT/PET is overlaid the CT scan, showing exactly where in the body a disease is located.

Other NM Procedures

Nuclear medicine is involved in more than just imaging procedures.

Radionuclide Therapy

It is oral, intravenous or intra-cavity administration of unsealed radioactive source for the preferential delivery of radiation to tumours.

In therapy, Ɣ-emitters would not treat a tumour*, just pass straight through it. Therefore β-emitters, α-emmiters and Auger electrons are more desirable as their effects stay localised to the tumour. Therapy radionuclides have a longer half-life than imaging radionuclides, as you want them to stay active for longer (usually days) and keep treating the tumour until it goes away. Therapy radionuclides also have a high activity and a mild toxicity (Nephrotoxicity, Bone marrow toxicity)

*However some therapy radionuclides are also Ɣ-emitters so they can be imaged at the same time

An example of a radionuclide is I-131 which is used for thyroid carcinoma. It has a very high activity greater than 1100 MBq and can go up to 10-20 GBq. The patient is usually discharged when activity is below specific limits (usually 800 MBq). Patients are advised to drink plenty of water and usually have a scan just before discharge.

SIRT Selective Internal Radiation Therapy

SIRT is used in inoperable liver cancer. Glass micro skewers (the size of red blood cells) contain radioactive materials. These are implanted into a liver tumour via an intra-arterial catheter placed into the hepatic artery under fluoroscopic control by interventional radiologist. They are not metabolised or excreted and stay trapped permanently in the liver. They decay with a physical life of ⁹⁰Y. Its administered activity is about 3 GBq and delivers doses from 200 - 600 Gy.

Sentinel lymph node procedures SLN

The sentinel lymph nodes (SLN) are the first lymph node(s) to which cancer cells are likely to spread from the primary tumour. SLN biopsy is used to determine the extent or stage of cancer. Because SLN biopsy involves the removal of fewer lymph nodes than standard lymph node procedures, the potential for side effects is lower. The best practice is to use combined techniques of injecting blue dye and radioactive tracer. The procedure involves the injection of radioactive tracer ^99mTc-Nanocolloid. 40 MBq if injected the day before surgery (preferable). 20 MBq if injected on the day of surgery.

SLN procedures are mostly used for breast cancers

In Vitro Glomerular filtration

This is where adult patients are injected with 10ml (2 MBq) of Chromium (Cr-51), and three blood samples are taken 2, 3 and 4 hours post the injection. The samples are then centrifuged with causing the plasma to separate from the red blood cells. Here we are looking at the renal function so the plasma is then sampled and counted with gamma counter. If the counts decrease after every hour then that shows that the patient has good renal clearance.