PET imaging Flashcards
What is catabolic metabolism?
Extraction of energy and reducing power from the environment
What is anabolic metabolism?
Macromolecule synthesis from simple biological building blocks
Which hallmark of cancer is caused by anabolic changes in a cancer cell
Enabling replicative immortality
What hallmark of cancer is caused by catabolic changes in a cell
Deregulating cellular energetics.
Which metabolic pathways are upregulated in cancer cells?
Oxidative phosphorylation and glycolysis
What advantage is gained by upregulation of glycolysis
glucose metabolism provides intermediates that feed into subsidary pathways. These include nucleic acid (PPP) and non essential amino acid production and TCA (krebs) pathways. All sustain proliferative signalling and resist death.
How does FDG get stuck in cells following uptake.
Uptake via Glut-1. It is then phosphorylated where it becomes stuck in the cell. This is because of the fluorine replacing the OH group, which is normally required for glucose to be transported for further glycolysis.
What gland shows FDG uptake?
Salivary
What effect does inflammation have on FDG uptake?
Inflammatory response to infection, chemo, surgery leads to high glucose metabolism
Why does inflammation cause a high uptake of FDG?
Inflammatory cells (T cells etc) begin to replicate very quickly at the site of inflammation. This requires high metabolism which increases FDG uptake.
What two reasons mean that FDG is not tumour specific?
1) Glut-1 may not be expressed on the tumour cells
2) Inflammatory cells and other metabolic organs exhibit FDG signalling.
What tumour types show low avidity for FDG?
Prostate tumours have very low Glut-1 expression.
What is the result of high glucose backgroun in FDG imaging?
Hard to delineate the tumour due to a lack of contrast in the image
What is the role of pyruvate kinase M2?
Catalyses the conversion of phosphoenolpyruvate to pyruvate by transfering the high energy phosphate group onto ADP to form ATP
Which spliceoform of PK is upregulated in all known cancers to date?
PKM2
What happens after the conversion of PEP into pyruvate?
It is a commitment step for the cell which will now undergo either glycolysis or oxidative phosphorylation of pyruvate.
In what structure does PK exist?
Tetramer
What effect does a PKM2 tetramer have on the choice of metabolic pathway?
Tetramer has high affinity for PEP which induces its conversion into pyruvate and the formation of ATP
What effect does a PKM2 homodimer have on the choice of metabolic pathway?
Homodimer of PKM2 has a lower affinity for PEP. This reduces glycolytic flux through pyruvate leading to the accumulation of precursors for biosynthesis of nucleic acids, phospholipids and amino acids.
What is the important role that PKM2 plays in normal cells with regard to anaboilc and catabolic pathways?
By switching between dimeric and tetrameric structures, the cell can decide if it is to undergo anabolic or metabolic pathways. Anabolic = dimer
catabolic = tetramer.
How does PKM2 expression change in cancer cells?
It is upregulated which causes anabolic pathways to produce macromolecules required for cellular proliferation
What is the problem with using PKM2 targeted PET-radiotracers?
whilst it does have good tumour uptake. There are combined excretion pathways in the kidney and bladder; but also in the liver and spleen. Therefore it cannot be used for body tumours
What tumour could PKM2 directed PET-radiotracers be used for imaging? (compared to FDG)
Brain tumours as it can pass through the BBB. This coupled with the fact that there is lower background noise in the brain compared to FDG makes it more suitable in this scenario.
What are the limitations of PKM2 tracers?
Tumour-to-muscle and blood background ratios are below those observed in FDG, this limits PKM2 to the brain.
Although PKM2 is tumour specific, PKM2 has the same low avidity in low GLUT-1 expressing tumours as FDG (prostate).
