Oxygen Enhancement Ratio and Radiation Response

Oxygen Enhancement Ratio (OER)

• OER is the ratio of doses under hypoxic to aerated conditions that produce the same biologic effect
• Oxygen presence (aerated cells) increases radiation effectiveness for cell killing
• Lack of oxygen (hypoxic cells) results in more radio-resistant cells
• Ionizing radiation at low LET is more effective in the presence of oxygen than in its absence in producing most biological effects
• The reciprocal of OER is Relative Radio-sensitivity, defined as 1.0 at 0% O2
• Most of the change in sensitivity occurs as oxygen tension increases from 0 to 30 mm Hg
• A further increase in oxygen content has little further effect

Response to Radiation

• Factors affecting radiation response include physical and biological factors
• Physical factors include linear energy transfer, relative biological effectiveness (RBE), fractionation and protraction
• Biological factors include oxygen effect, phase of cell cycle, ability to repair, chemical agents, and hormesis

Nature of the Oxygen Effect

• Cells are more sensitive to x-rays in the presence of oxygen than in its absence (hypoxia)
• OER is the ratio of doses under hypoxic to aerated conditions required to produce the same level of cell killing
• High-dose assay results in OER = 3.5
• Low-dose assay results in OER = 2.5

Oxygen Effect Details

• Molecular oxygen must be present during radiation exposure to fix damage
• Oxygen makes damage permanent, produced by free radicals
• In the absence of oxygen, damage may be repaired
• Free-radical reactions involve functional groups with oxygen forming organic peroxides, fixing indirect damage
• Oxygen has no impact on direct damage

OER and LET

• OER varies from 2-3, increasing with dose
• Low-LET radiations have a more pronounced oxygen effect
• High-LET radiations have a non-existent oxygen effect (OER = 1)
• OER is calculated as De(red.O2)/ De(air)

Other Radiations and OER

• OER values for 15 MeV Neutrons = 1.6
• OER values for α particles = 1.0

OER and Linear Energy Transfer (LET)

• At low LET (x- or γ-rays), OER is between 2.5 and 3
• As LET increases, OER falls, reaching unity when LET is about 200 keV/µm

OER & RBE as a function of LET

• OER and RBE are virtually mirror images of each other as a function of LET
• Optimal RBE and rapid fall of OER occur at approximately 100 keV/µm

Tumor Hypoxia

• Tumor size and vascularity affect oxygen diffusion
• The distance oxygen can diffuse is about 70 μm at the arterial end of a capillary and less at the venous end
• In tumors, cells that are > 70 μm become hypoxic
• Acute hypoxia is the result of temporary closing of tumor blood vessels
• Chronic hypoxia occurs due to poor vasculature in tumors
• There is evidence that hypoxia plays a role in radioresistance, malignant progression, and metastasis

Reoxygenation

• Hypoxic tissues are more resistant to radiation
• Tumor cells become better oxygenated after irradiation, due to easier access, because surrounding cells have died
• As a consequence, tumoral cells become more radiation sensitive
• Immediately after irradiation, most tumor cells become hypoxic
• By 6 hours, the percentage of hypoxic cells falls to pre-irradiation level

Conclusion

• OER is the ratio of hypoxic-to-aerated doses
• OER decreases as LET increases
• Oxygen must be present during irradiation, or very soon after(microseconds)
• Very little oxygen is required (<5%)