T O P I C A L C A S E 1 – L A C K I N G O X YG E N
learning goals
1. what is hypoxia and how does a hypoxic tumour behave?
2. answer the following questions about the sugar scan:
a) why did they use a sugar scan and what scan did they use?
b) what did they target?
c) what are the results and what do the results of a hypoxia patient look like
when using this scan?
3. answer the following questions about the nitroimidazole scan:
a) why did they use this scan?
b) what did they target?
c) what are the results and what do the results of a hypoxia patient look like
when using this scan?
d) what type of radioactive tracers are used in hypoxic patients?
home study
hypoxia and hypoxic tumours
normally there is a steady state of oxygen concentration in tissues --> balance between
supply and demand. however, sometimes this equilibrium is disturbed and the oxygen
concentration in a tissue becomes too low. the cells of tissue lack oxygen and are in a
state of trying to survive, this is called hypoxia.
o hypoxia = below-normal oxygen level
in normal tissues, blood vessels are arranged in a controlled and systematic manner -->
the distance from the cells to the capillaries establish a constant and uniform oxygen
gradient.
tumour vasculature
abnormal vasculature is the prime cause of hypoxia in tumours
o impaired and chaotic blood vessel development
o tumour cells outgrow the blood supply
o tumour blood vessels are also unstable and might collapse --> causing (temporary)
occlusion
therefore, lack of oxygen supply --> regions of hypoxia [1, 2].
, hypoxia in tumours
Tumour cell hypoxia decreases the effectiveness of anti-cancer treatment and increases
tumour aggressiveness in a number of solid tumours [3]. tumours hypoxia influences
malignancy by adapting via several mechanisms:
o increased anaerobic glycolysis and angiogenesis
o natural selection --> only cells that can cope with low oxygen survive, creating a
more malignant phenotype
o hypoxia can alter the DNA repair capacity --> promoting genomic instability -->
can accelerate cancer development [4]
there are two kinds of hypoxic tumours
1. chronic hypoxia --> diffusion-limited hypoxia
▪ tumour growth cause limited oxygen diffusion
- blood vessels in the tumour are surrounded by proliferating cells
until the diffusion barrier is reached
- the proliferating cells are surrounded by hypoxic cells
2. acute hypoxia --> perfusion-limited hypoxia
▪ temporally unstable blood flow leads to fluctuating perfusion-limited
hypoxia
- (temporary) non-functional blood vessel is surrounded by hypoxic
cells
also, due to the lack of oxygen hypoxic tumours are more resistant to treatment (e.g.
radiotherapy).
learning goals
1. what is hypoxia and how does a hypoxic tumour behave?
2. answer the following questions about the sugar scan:
a) why did they use a sugar scan and what scan did they use?
b) what did they target?
c) what are the results and what do the results of a hypoxia patient look like
when using this scan?
3. answer the following questions about the nitroimidazole scan:
a) why did they use this scan?
b) what did they target?
c) what are the results and what do the results of a hypoxia patient look like
when using this scan?
d) what type of radioactive tracers are used in hypoxic patients?
home study
hypoxia and hypoxic tumours
normally there is a steady state of oxygen concentration in tissues --> balance between
supply and demand. however, sometimes this equilibrium is disturbed and the oxygen
concentration in a tissue becomes too low. the cells of tissue lack oxygen and are in a
state of trying to survive, this is called hypoxia.
o hypoxia = below-normal oxygen level
in normal tissues, blood vessels are arranged in a controlled and systematic manner -->
the distance from the cells to the capillaries establish a constant and uniform oxygen
gradient.
tumour vasculature
abnormal vasculature is the prime cause of hypoxia in tumours
o impaired and chaotic blood vessel development
o tumour cells outgrow the blood supply
o tumour blood vessels are also unstable and might collapse --> causing (temporary)
occlusion
therefore, lack of oxygen supply --> regions of hypoxia [1, 2].
, hypoxia in tumours
Tumour cell hypoxia decreases the effectiveness of anti-cancer treatment and increases
tumour aggressiveness in a number of solid tumours [3]. tumours hypoxia influences
malignancy by adapting via several mechanisms:
o increased anaerobic glycolysis and angiogenesis
o natural selection --> only cells that can cope with low oxygen survive, creating a
more malignant phenotype
o hypoxia can alter the DNA repair capacity --> promoting genomic instability -->
can accelerate cancer development [4]
there are two kinds of hypoxic tumours
1. chronic hypoxia --> diffusion-limited hypoxia
▪ tumour growth cause limited oxygen diffusion
- blood vessels in the tumour are surrounded by proliferating cells
until the diffusion barrier is reached
- the proliferating cells are surrounded by hypoxic cells
2. acute hypoxia --> perfusion-limited hypoxia
▪ temporally unstable blood flow leads to fluctuating perfusion-limited
hypoxia
- (temporary) non-functional blood vessel is surrounded by hypoxic
cells
also, due to the lack of oxygen hypoxic tumours are more resistant to treatment (e.g.
radiotherapy).
