Radioactively Labelled Tracers

The radioisotope fluorine-18 is the most frequently used isotope for PEPT studies. Fluorine-18 decays by positron emission resulting in stable oxygen-18. The nucleus of fluorine-18 is unstable as it is proton rich, as such; a proton converts to a neutron and emits a positron and neutrino. A positron is an antimatter particle which is similar to an electron but has a positive charge.

Diagram of Fluorine18 chemical reaction

The emitted positron travels a short distance, comes to rest and then annihilates with a nearby electron. The mass of the two particles is converted to energy in the form of two 511keV gamma photons that are emitted back-to-back, 180º apart. These photons are detected simultaneously by the PEPT camera system and the particle path tracked in 3D.

Fluorine-18 is produced in the MC40 Cyclotron using the ion beam helium-3. The helium-3 beam interacts with oxygen and converts it to radioactive fluorine by the following reaction; ¹⁶O(³He, p)¹⁸F.

A multitude of tracer particles can be used in PEPT studies depending on the individual project. Generally the size range is 100µm – 10mm. In actuality there is no upper limit to the size of the particle that can be labelled, however for large particles the distribution of activity must be considered. Tracking a localised spot of activity on the surface of a large particle leads to a track which is sensitive to the rotation of the particle as well as its translational motion. 

For some applications there is a demand for very small tracer particles that are ≤100µm. This is possible however the process is limited by the difficulties of handling such particles. 50µm has been achieved in previous studies and the most likely limit due to the capacity of the particle to hold the activity is 10µm. Working towards using very small particles is part of the ongoing research within the Centre. 

There are generally two methods used to activate tracer particles depending on their size and properties:

Direct Activation

Particles that are ≥1mm, have a melting point above 1400°C and contain some form of oxygen can be placed directly in the cyclotron beam to be activated. Some of the oxygen within the particle is converted to fluorine-18 and the particle can then be used for PEPT.

Indirect Activation

Particles that are ≤1mm or have low melting points and some affinity for fluoride ions can be indirectly activated. The cyclotron beam irradiates deionised water, converting some of the oxygen within it to fluorine-18. The tracer particles are then immersed in the ‘activated water’ and the water is slowly evaporated around them. During this evaporation process a proportion of the fluorine-18 ions attach to the tracer particles.

When using indirect activation the fluorine-18 ions are generally adsorbed onto the surface of the tracer particle. Fluoride ions are very reactive, as such if the tracer particle is exposed to aqueous solution the fluoride ions tend to leach from the particle and contaminate the system. If the tracer is to be used in wet conditions it must first be sealed which is generally done using acrylic paint. This process is cumbersome for smaller particles and a weakness of this method. Innovative coating methods are part of the ongoing research at the Centre to overcome this barrier.

The activity required for a PEPT tracer depends upon the speed at which it will be travelling and the attenuating material through which the photons have to pass to be detected. As the mass of material surrounding the tracer increases, the required activity increases correspondingly. In turn, the faster the tracer will be travelling, the further that particle travels in a second. Therefore the location data becomes less accurate, corresponding to a higher required activity. (It should also be noted that the detection of particles is limited by the camera capabilities (please see ADAC Forte Positron Camera and Modular Positron Camera for more information).

The types of particles that can be activated include:

  • Glass beads (¹⁸F)
  • Silica (¹⁸F)
  • Alumina (¹⁸F)
  • Steel beads (⁵⁵Co)
  • Copper beads (⁶⁴Cu)
  • Hydroxyapatite (¹⁸F)
  • Sand (¹⁸F)
  • Zirconia (¹⁸F)
  • Ion exchange resins (¹⁸F)
  • Delrin (¹⁸F)
  • Nylon (¹⁸F)

This list is not exhaustive. Please If you're interested in using this service, please contact us to discuss further.