How to develop PET tracer Flashcards
Name the 5 steps in the process of tracer synthesis (broadly).
- Irradiation
- Convert radionuclide into labeling synthon
- Labelin reaction
- Purification
- Formulation
What is a cyclotron (used for)?
A cyclotron is a particle accelerator where charged particles (ions) are accelerated by applying an electric field across the gap. With the increasing speed, the charged particles will follow the path of the cyclotron and will eventually reach maximum speed. At this point, the charged particle will be converted into a proton. The proton will ‘fly off track’. By letting the proton collide with a molecule of choice, a nuclear reaction is started. With this, radionuclides can be created like 18-F.
The basic characteristics of all cyclotrons are the same. There is an ion source to produce ions, an acceleration chamber to accelerate them and a magnet to contain the ions on a circular path.
What is a big challenge regarding the use of radionuclides for PET imaging?
The often short half-lives of the radionuclides.
A fluid radionuclide target is 18-F. What is an advantage and disadvantage of this radionuclide?
Advantage:
- relatively long half-life
Disadvantage:
- normally not present in the body, so if the radionuclide is adhered to a tracer (such as estrogen), the natural form of the tracer is changed.
A gas radionuclide target is 11-C. Name advantages and disadvantages of this radionuclide.
Advantage:
- C is already present in our bodies, so adhering this radionuclide to a tracer is relatively easy and it doesn’t change the natural properties of the tracer
Disadvantage:
- relatively short half-life (60 mins)
A solid radionuclide target is 89-Zr Name advantages and disadvantages of this radionuclide.
Advantage:
- it is frequently used to adhere the radionuclide to antibodies. Antibodies often have slow uptake in the body, so a radionuclide is needed with a longer half-life, which is the case for 89-Zr.
Disadvantage:
- it is radioactive for multiple days
- development of 89Zr-antibody complex is labour intensive
So for the development of PET tracers, you must work with radioactivity. What safety measurements can be taken to minimize radiation exposure?
- 6 cm lead shielding
- Special hot cells (e.g. where the pressure is higher in the hot cells than on the outside, so that substances cannot escape easily)
- Sufficient ventilation
- Shielding
Why are you always able to only produce 40% radioactivity of a certain radionuclide?
Because radionuclides have their half-lives, which causes the maximum chemical yield to not be equal to the maximum radiochemical yield.
It implies that if you want 100% of the chemical yield, it would take 90 minutes to produce 100%. However, in those 90 minutes that radiochemical yield decreases quickly. So you have to stop the chemical yield at the moment there is already maximum radiochemical yield, which is around 40%.
What is the only way to increase the maximum radiochemical yield (by just a bit)?
To increase the reaction speed of the reaction (fast kinetics). This will result in a maximum radiochemical yield of 50% (instead of 40%), but it will decrease the maximum chemical yield (80 instead of 100%).
Erlotinib is a drug that fights cancer (in lung and pancreas). The drug targets patients with an EGFR mutation and thus the drugs binds to the EGFR. Before administering the drug, you want to know if the drug will work in a specific patient. How would you do this?
By developing a [11C]erlotinib PET scan, where you can first scan if erlotinib interacts in the body before starting the therapy.
Tumor cells will sometimes express PD-L1. What is the effect of the expression of PD-L1 on tumor cells?
T-cells can bind with PD-1 to PD-L1 on tumor cells, which causes the inhibition of the T cells so that the T cells cannot fight the tumor cells.
Nivolumab is an antibody that targets PD-1 on T-cells, which prevents inhibition of T-cells by binding of PD-L1 of tumor cells. Therefore, nivolumab will only work if the tumors expresses PD-L1. This can be researched by taking a biopt and applying immunohistochemistry on it. What is the downside of this?
That in 10% of cases where PD-L1 is not found in immunohistochemistry (and it is expected that nivolumab won’t work), PD-L1 is actually present (i.e. false-negative).
Nivolumab is an antibody that targets PD-1 on T-cells, which prevents inhibition of T-cells by binding of PD-L1 of tumor cells. Therefore, nivolumab will only work if the tumors expresses PD-L1. This can be researched by taking a biopt and applying immunohistochemistry on it. What is another way of researching this?
Using [89Zr]nivolumab PET
What is the biggest disadvantage of PET (tracer development)?
- Costs
- Capacity for PET techniques
