Radiopharmaceuticals consist of a radioactive isotope, which creates the image, and a pharmaceutical, which determines the physiological behaviour of the compound and, therefore, where the signal accumulates to form the image.
There are several properties of the ideal radioisotope for diagnostic purposes (i.e. not therapeutic):
- Half life which is short enough to limit radiation dose to patient but long enough to allow good signal during imaging (ideally 1.5 x length of imaging)
- Emits gamma rays which are of high enough energy to leave the body, reach the camera and contribute to the image. The low energy of alpha or beta particles means they are absorbed by the body which increases the radiation dose to the patient and limits the radiation that reaches the camera to produce the image
- Mono-energetic gamma emitter (i.e. gamma rays of one energy). The ideal energy range is 100 to 250 keV for optimal imaging
- Decays to stable daughter isotopes that will not cause significant radiation dose to patient
- Easy to bind to different pharmaceuticals
- Doesn't change behaviour of pharmaceutical
And there are several properties of the ideal pharmaceutical:
- High target:non-target uptake ratio
- Easy and cheap to produce
- Does not alter physiology in order to give accurate depiction of patient's physiology
There are three methods for producing radioisotopes:
- Nuclear reactor
- Radionuclide generator
This method of producing radioisotopes is also called nuclear bombardment.
- The cyclotron consists of a vacuum chamber into which particles are injected into the centre
- These are accelerated in a circular path by a high frequency alternating voltage applied between two D-shaped electrodes (these are called "dee's"). The dee's are hollow and allow the particles to move between them
- The particles are then made to move in a spiral pattern from the centre of the vacuum chamber to the outside by applying a large static magnetic field
- As the particles' path leads them to the edge of the cyclotron they eventually enter the bombardment chamber and interact with the target to produce the radioisotopes.
Cyclotron produced radioisotopes
- Fluorine-18 - used in FDG PET scanning as well as with choline. Created by bombarding 18O rich water with protons to produce 18F. 18F has a half-life of 1.87 hours and releases gamma rays with an energy of 511 keV.
- Gallium-67 - used as 67Ga-citrate for imaging of inflammation / tumours
- Thallium-201 - used as 201Tl-chloride in cardiac function imaging
- The core of 235Uranium undergoes spontaneous fission into lighter fragments emitting two or three fission neutrons in the process
- These fission neutrons then interact with 235U to produce the highly unstable 236U which carries on the fission event in a self-sustaining nuclear chain reaction
- Materials can be lowered into ports in the reactor to be irradiated by the neutrons. Neutron capture then creates isotopes of the target element
The fission activity can be controlled with control rods that engulf the cores and are made of material that absorbs the neutrons without undergoing fission (e.g. cadmium or boron) preventing further fission events.
The moderator rods are made of a material that slows down the energetic fission neutrons. Slower neutrons are more efficient at initiating additional fission events.
Radionuclides produced by neutron activation
- Neutrons are added to isotopes creating a heavy isotope that generally lie above the line of stability. This means they tend to decay in B- emission
- Only a very small fraction of the target nuclei are activated
- A disadvantage of a nuclear reactor is the relatively low yield of the desired radioisotope and the substantial production of other radioisotopes.
Reactor produced radioisotopes
- Technetium-99m - used in 80% of nuclear medicine studies.
- Iodine-131 - used in treating and in imaging the thyroid gland
- Xenon-133 - used in lung ventilation studies. Half-life of 5 days so can be transported readily unlike krypton-81m
- A slow-decaying parent radionuclide is adsorbed onto a surface such as alumina in a sterile glass column encased in a lead or depleted uranium shield
- This parent radionuclide decays into the shorter-lived radionuclide that will be used for the nuclear imaging - the "daughter" radionuclide
- The "daughter" radionuclide is removed by passing an eluting solvent (such as sterile saline) through the glass column
- The resulting solution is collected into a vial which collects the daughter solvent via a vacuum action
This method of producing radionuclides is useful when using a short lived radionuclide as it needs to be produced near the patient. In this way the generator can travel whilst producing the daughter radioisotope to the site of use at which point it can be eluted. Each time the radioisotope is eluted its activity (concentration) drops to zero. It then steadily builds up again until it is eluted again.
Generator produced radionuclides
Technetium-99m, the most commonly used radioisotope, is produced in this way from the longer-lived Molybdenum-99 (created by nuclear reactors) which decays via beta decay.
Another radioisotope produced by this method is Krypton-81m, used in lung ventilation studies.
- Rubidium-81 is produced by a cyclotron
- Adsorbed onto zirconium phosphate in the generator
- Decays into Krypton-81m by electron capture and beta decay
- Krypton-81m is then extracted from the column by blowing air through it
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- Radiopharmaceutical = radioistope (releases radioactivity imaged) + pharmaceutical (determines where radioactivity accumulates)
- Ideal radioisotope
- Half life short enough to limit radiation dose but long enough for good signal during imaging
- Emits gamma rays (high energy, leave patient) not alpha or beta (low energy, do not leave patient)
- Decays to stable daughter isotope
- Easy to bind to pharmaceutical
- Does not alter activity of pharmaceutical
- Ideal pharmaceutical
- High target:non-target uptake ratio
- Easy and cheap to produce
- Doesn't alter patient physiology
- Particles injected into centre
- Accelerated in spiral path to the outside by Dee electrodes and static magnetic field
- Enter bombardment chamber and interact with target to produce radioisotopes
- Products: Fluorine-18, Gallium-67, Thalium-201, Krypton-81m
- Core Uranium-235 undergoes spontaneous fission releasing neutrons
- Neutrons interact with Uranium-236 to induce further fission - chain reaction
- Materials lowered into ports to be irradiated by neutrons and converting into desired isotope
- Fission activity controlled by control rods that cover uranium rods and absorb fission neutrons to prevent interaction with uranium-236
- Moderator rods slow down energetic fission neutrons to make fission more efficient
- Products: Technetium-99m, Iodine-131, Xenon-133
- Parent radionuclide adsorbed onto surface e.g alumina in a glass column. Decays into daughter nuclide
- Daughter nuclide removed by passing solvent through the glass colum
- Eluted daughter activity collected in vial via vacuum action
- Products: Technetium-99m, Krypton-81m