OER   :   OXYGEN ENHANCEMENT RATIO

The ratio of the reaction of cells to dose without oxygen versus with oxygen

(OER = hypoxic  / oxic)

• Will alter cell survival curve
• Is considered a chemical modifier (Oxygen is a chemical)
• It is a radiosensitizer (increases response to radiation)
• Oxygen is the best radiosensitizer we have for LOW LET radiation
• Is also know as the universal sensitizer / oxygen effect

Oxic – cells that are fully oxygenated

Hypoxic – cells that have a little ozygen

Anoxic – cells that have no oxygen (DEAD)

Oxygenated tissue is 3 times more responsive than hypoxic cells to radiation

• This is the reason we fractionate – to give the hypoxic tissue of the tumor a  chance to become oxic (oxygenated),  through the blood supply,  and therefore it will become more radiosensitive (3x than is was as hypoxic tumor cells).  This is possible with fractionation because after we irradiate and the oxic cells of the tumor die, they will peel away revealing the hypoxic tumor cells underneath them to the blood supply which will oxygenate them.
• Also protects normal tissue

Why is oxygen so important?

• Because of the Free Radicals and Ions.  (we need oxygen to produce these) , especially the hydroxyl free radical which does the most damage
• If oxygen is present in tissue the oxygen combines with free radicals to make RADICAL PEROXIDE (has 2 oxygen atoms)
• Oxygen makes the free radicals live longer

“fixing” or “making permanent” the damage – terms used to to describe oxygens effect on free radicals where it helps them to stay as free radicals and will not recombine

OXYGEN MUST BE PRESENT AT THE TIME OF IRRADIATION FOR THIS TO HAPPEN!!!

*Radical scavengers – eat up free radicals.  Sometimes patients are injected with Amifostine which will eat up the free radical.

This is an example of a cell survival curve of  Same Type of Cells irradiated with X-Rays:

• Cells that are without oxygen have a shallow curve
• Cells that are oxygenated have a steeper curve

The next 2 cell survival curves we see Same Type Cells with different types of radiation (higher LET).  As you can see as the LET gets higher oxygen plays less and less of a role and eventually as in the last graph with Alpha Rays there is no effect at all with oxygen as compared without oxygen:

• In the case where there is no effect due to oxygenation the OER would be = 1 (the curves are said to be in Unity)
• The reason why x-rays and gamma rays are effected and higher LET is not is x and gamma rays depend on oxygen for the formation of free radicals.  X and Gamma rays kill by the indirect effect
• Higher LET radiation such as electrons, betas, neutrons, protons and alphas kill by the more direct effects of radiation therefore donot rely on oxygen or their products being free radicals.

The next graph represents OER as we Increase LET:

• Oxygen plays a less important role as LET increases

The next graph represents both RBE and OER as compared to LET

• OER goes down as the LET gets higher
• RBE goes up as LET gets higher until it reaches the LET of alphas (110 kev/u); this point will be the point of Maximum RBE; after this there is a falloff in RBE because LET is so high that there will be wasted dose and is too high to kills cells which causes it to loose it effectivness

Bi – Phasic Curve – the proportion of hypoxic cells to oxygenated cells increases in the way where the Initial Response to the dose of radiation is good because the outer layer is oxygenated but as those cells are killed and we peel back to the more hypoxic cells now these hypoxic cells respond differently than the onxygenated cells and will be killed more slowly therefore the slope is more shallow(tumor cells)

Hypoxic Component of Tissue – can be back extrapolated from the point where the initial change from oxygenated to hypoxic cells takes place on the curve.  This point will back extraplolate to the percentage of cells that are hypoxic

Example of Bi Phasic Curve